www.22sbc.com_www.22sbc.com-【让你轻松】:江淮iEVS4更多官图发布上海车展上市

www.22sbc.com_www.22sbc.com-【让你轻松】

2019-10-24 09:37:52

字体:标准

  Toexpressourappreciation,MSDbegan#DearCancerHeroes–asocialmediacampaigntorecognizetheirfortitudeandcontributionstothefield.It’sasmallgesturetoshowourgratitude.Wewanttoletclinicaltrialparticipantsknowtheyarenotaloneandthereisawholecommunityofpeoplecheeringthemon.Anyonecanjointhemovementbywritingamessagetocancerclinicaltrialparticipantsonastickynoteandsharingitonsocialmediausing#DearCancerHeroes.Cancerresearchhascomealongwayandstillhasalongwaytogo.However,wewouldn’thavegottentowherewearetodaywithouttheseheroes.Toexpressourappreciation,MSDbegan#DearCancerHeroes–asocialmediacampaigntorecognizetheirfortitudeandcontributionstothefield.It’sasmallgesturetoshowourgratitude.Wewanttoletclinicaltrialparticipantsknowtheyarenotaloneandthereisawholecommunityofpeoplecheeringthemon.Anyonecanjointhemovementbywritingamessagetocancerclinicaltrialparticipantsonastickynoteandsharingitonsocialmediausing#DearCancerHeroes.Cancerresearchhascomealongwayandstillhasalongwaytogo.However,wewouldn’thavegottentowherewearetodaywithouttheseheroes.Toexpressourappreciation,MSDbegan#DearCancerHeroes–asocialmediacampaigntorecognizetheirfortitudeandcontributionstothefield.It’sasmallgesturetoshowourgratitude.Wewanttoletclinicaltrialparticipantsknowtheyarenotaloneandthereisawholecommunityofpeoplecheeringthemon.Anyonecanjointhemovementbywritingamessagetocancerclinicaltrialparticipantsonastickynoteandsharingitonsocialmediausing#DearCancerHeroes.Cancerresearchhascomealongwayandstillhasalongwaytogo.However,wewouldn’thavegottentowherewearetodaywithouttheseheroes.

  CarolineFox,M.D.ispassionateaboutgenetics.Inmedicalschool,shestudiedtheeffectsoftheenvironmentondiabetesandobesityonatribeofNativeAmericans(certainpopulationsworldwidehaveagreaterpropensitytowardsdiabetes;thistribewasonesuchgroup).Herresearchlefthermotivatedtolearnmoreabouthowgeneticsplaysaroleinmetabolicdiseases.Thatwasmystart,shenotes.Sincethen,almostallofmyresearchhasbeenfocusedonuncoveringthegeneticfoundationsofthesetypesofdiseases.ChangingPerceptionsPriortojoiningMSDResearchLaboratoriesinBoston,CarolineworkedattheNationalInstitutesofHealth.There,sheledalabthatstudiedmetabolicriskfactorsforcardiovasculardiseaseaspartofthe,apioneeringlong-termpopulationstudyofcardiovasculardisease.But,shenotes,theshifttoMSDwasarelativelyeasyone.IwasimpressedbyMSDseffortstoleveragehumangeneticstodrivedrugdiscovery,shesays.Forme,itwastheperfectnextstepfromtheworkthatIhadbeendoinginacademia.Genetics:TheNewFrontierWe'relucky—CarolinespassionforgeneticsisagreatfitforMSD.Inourlabsandacrosstheindustry,weareseeinganincreaseduseofhumangeneticstohelpdeterminewhetherpatientswillrespondtoacertaindrugornot,ShepointstoMSD'sactiveresearchcollaborationswithscientistsaroundtheworldaimedatadvancingthisfieldofscience.Iamveryenthusiasticaboutwhereourresearchmaylead.Historically,oncologypracticeandclinicaltrialdesignprimarilyfocusedonwherethetumorfirstemerged,suchascolonorrectum,lung,breast,andendometrium.Thisapproachfollowsthelogicofthescalpel:pinpointingthelocationofthetumorfirstenabledsurgicalplans.Morerecently,therehavebeensignificantadvancesinourunderstandingoftheroleofcancerbiomarkersinmolecularandcellularmechanismsthatcandrivetumorgrowth.Biomarkersarebiologicalmolecules(typicallycomprisedofDNA,RNAorprotein)foundintissuesorbloodthatcanserveasasigntobetterunderstandaconditionordisease.Sometimes,thesamebiomarkerisfoundacrossmanydifferenttypesofcancer,regardlessofwherethetumorfirstdeveloped.Withinaspecifictumorlocation,thesebiomarkerscansometimesdifferentiatewhetherthetumorislikelytorespondtoagiventreatment.Assuch,thesebiomarkershavebeenusedtohelpinformclinicalresearch,acceleratingtheprocessofgettingtargetedmedicinestopatientswhereseparatetrialswouldtakeyearstoconduct.Importantly,insomecases,thesefeaturescanbeassessedusinglaboratoryteststhathavelongbeenavailable.Whereatestiseithernotavailable,orforresearchuseonly,thetestmanufacturerpartnerswiththedrugmanufacturertoadvancetogetherintoregulatoryapprovalbygovernmentagencies(suchastheFDA)acompaniondiagnosticassaytoensuresafeandeffectiveuseofthedruginpatientslikelytorespond.Thegoalistouseadeeperunderstandingofthetumorbiologyandassociatedbiomarkerstotackletumorresearchmoreprecisely;goingbeyondsimplywhereatumorarose.Instead,wearelearninghowtoattackacancerbasedonitsbiologyatthecellularlevel.AtMSD,effortsareunderwaytobetterunderstandmicrosatelliteinstability(MSI)andmismatchrepairdeficiency(dMMR).Thesebiomarkersarepresentacrosstumortypes,regardlessoftheoriginallocationofthecancer.ThepresenceofhighlevelsofMSI(MSI-H)ordMMRsignifiesanunderlyingprobleminacell'sabilitytofixerrorsthatoccurwhenDNAreplicates.TumorcellsdeterminedtohaveMSI-HordMMRharborhundredstothousandsofmutations.Theultimateproofofoureffortswillmanifestasanewgenerationofcancermedicines:thosethatfollowthelogicofbiology,notthelogicofthescalpel.Chemistryhasbeencentraltoourbusinessofsinceourearliestdaysasacompany.Historically,ourdrugdiscoveryprocessprimarilycenteredaroundsmallmolecules.Then,thebirthofbiotechnologyinthelate1970s/early1980saddedbiologics,orengineeredproteins,tothemix.Today,newmodalitiesareemergingthatshowastrongpotentialtotargetcomplexdiseasesthathavenotyetbeenreachablewitheithersmallmoleculesorbiologics.RobGarbaccioisleadingatalentedteamofchemistswhoarehelpingguideMSD’sentryintothisexcitingnewfieldofmedicine.IntroducinganddiscoveringnewwaysforwardRobistheassociatevicepresident,ChemistryCapabilitiesforAcceleratingTherapeutics(CCAT),adiscoverychemistryteamthatislookingathowtogobeyondthetraditionalmethodsofdiscoveringanddevelopingmedicines."Therearecertaindiseasetargetsthatarereallyhardto'reach'andimpactusingtraditionalmethods,"henotes."SopartofthegroupIoverseetriestofigureouthowwecanemploynewermodalities,suchaspeptides,bioconjugates,andoligonucleotides,toaddressthechallengingtargetsthatareincreasinglyemergingfrombiologicalresearch."Rob'sgroupisnotfocusedonanyspecifictherapeuticarea--theyareseekingnewwaystoaddressthemostdifficultdiseasetargets."Inoncology,infectiousdiseases,andneuroscience,forexample,we’relookingforthosetargetsthatourcolleaguessay,'Ifonlywecouldmodulatethistarget,webelievewemightbeabletopotentiallyinterruptthediseaseprocessandhelppatients,'"henotes.Using‘creativechemistry’totreatdiseaseIt'scomplexwork,tobesure,butthat'swhatmakesitsointriguingandinspiringforRobandhisteam."ThethingthatIlikethemostaboutmyworkisthebeliefthattheremaybeapathforwardforthetreatmentofeachandeveryoneofthesediseases.Wejustcan'tseeityetbecausethebiologyissocomplex,"saysRob."Asresearcherscontinuetoimproveourunderstandingofdiseasebiology,Ibelievethatcombiningthatknowledgewithcreativechemistrywillhelpleadusdownnewroadstotreatingdiseaseandhelpingpatients."Robjoinedthecompanyaftercompletinggraduateschoolandapostdoctoralfellowshipfocusingonorganicchemistry."Icameherebecausescienceandinnovationdrivethiscompany.I'mpassionateaboutourmissiontosaveandimprovelives,andIbelievethatmybestdayatwork,thedaymyteammakesapotentiallylife-changingdiscovery,isstillaheadofme,andit'sthereasonthatIstay."InventingforlifeAtMSD,wesayweare.AndRobdefinitelyseeshimselfasaninventor."Chemistshavethisuniqueabilitytocombineatomsandbondsbetweenatomsinauniqueway.Everydaychemistsareinventinghundredsofmoleculesthathaveneverexistedbefore.So,yes,weareinventing,"hesays."Weareinventingtosolveproblems."

  CarolineFox,M.D.ispassionateaboutgenetics.Inmedicalschool,shestudiedtheeffectsoftheenvironmentondiabetesandobesityonatribeofNativeAmericans(certainpopulationsworldwidehaveagreaterpropensitytowardsdiabetes;thistribewasonesuchgroup).Herresearchlefthermotivatedtolearnmoreabouthowgeneticsplaysaroleinmetabolicdiseases.Thatwasmystart,shenotes.Sincethen,almostallofmyresearchhasbeenfocusedonuncoveringthegeneticfoundationsofthesetypesofdiseases.ChangingPerceptionsPriortojoiningMSDResearchLaboratoriesinBoston,CarolineworkedattheNationalInstitutesofHealth.There,sheledalabthatstudiedmetabolicriskfactorsforcardiovasculardiseaseaspartofthe,apioneeringlong-termpopulationstudyofcardiovasculardisease.But,shenotes,theshifttoMSDwasarelativelyeasyone.IwasimpressedbyMSDseffortstoleveragehumangeneticstodrivedrugdiscovery,shesays.Forme,itwastheperfectnextstepfromtheworkthatIhadbeendoinginacademia.Genetics:TheNewFrontierWe'relucky—CarolinespassionforgeneticsisagreatfitforMSD.Inourlabsandacrosstheindustry,weareseeinganincreaseduseofhumangeneticstohelpdeterminewhetherpatientswillrespondtoacertaindrugornot,ShepointstoMSD'sactiveresearchcollaborationswithscientistsaroundtheworldaimedatadvancingthisfieldofscience.Iamveryenthusiasticaboutwhereourresearchmaylead.Toexpressourappreciation,MSDbegan#DearCancerHeroes–asocialmediacampaigntorecognizetheirfortitudeandcontributionstothefield.It’sasmallgesturetoshowourgratitude.Wewanttoletclinicaltrialparticipantsknowtheyarenotaloneandthereisawholecommunityofpeoplecheeringthemon.Anyonecanjointhemovementbywritingamessagetocancerclinicaltrialparticipantsonastickynoteandsharingitonsocialmediausing#DearCancerHeroes.Cancerresearchhascomealongwayandstillhasalongwaytogo.However,wewouldn’thavegottentowherewearetodaywithouttheseheroes.Chemistryhasbeencentraltoourbusinessofsinceourearliestdaysasacompany.Historically,ourdrugdiscoveryprocessprimarilycenteredaroundsmallmolecules.Then,thebirthofbiotechnologyinthelate1970s/early1980saddedbiologics,orengineeredproteins,tothemix.Today,newmodalitiesareemergingthatshowastrongpotentialtotargetcomplexdiseasesthathavenotyetbeenreachablewitheithersmallmoleculesorbiologics.RobGarbaccioisleadingatalentedteamofchemistswhoarehelpingguideMSD’sentryintothisexcitingnewfieldofmedicine.IntroducinganddiscoveringnewwaysforwardRobistheassociatevicepresident,ChemistryCapabilitiesforAcceleratingTherapeutics(CCAT),adiscoverychemistryteamthatislookingathowtogobeyondthetraditionalmethodsofdiscoveringanddevelopingmedicines."Therearecertaindiseasetargetsthatarereallyhardto'reach'andimpactusingtraditionalmethods,"henotes."SopartofthegroupIoverseetriestofigureouthowwecanemploynewermodalities,suchaspeptides,bioconjugates,andoligonucleotides,toaddressthechallengingtargetsthatareincreasinglyemergingfrombiologicalresearch."Rob'sgroupisnotfocusedonanyspecifictherapeuticarea--theyareseekingnewwaystoaddressthemostdifficultdiseasetargets."Inoncology,infectiousdiseases,andneuroscience,forexample,we’relookingforthosetargetsthatourcolleaguessay,'Ifonlywecouldmodulatethistarget,webelievewemightbeabletopotentiallyinterruptthediseaseprocessandhelppatients,'"henotes.Using‘creativechemistry’totreatdiseaseIt'scomplexwork,tobesure,butthat'swhatmakesitsointriguingandinspiringforRobandhisteam."ThethingthatIlikethemostaboutmyworkisthebeliefthattheremaybeapathforwardforthetreatmentofeachandeveryoneofthesediseases.Wejustcan'tseeityetbecausethebiologyissocomplex,"saysRob."Asresearcherscontinuetoimproveourunderstandingofdiseasebiology,Ibelievethatcombiningthatknowledgewithcreativechemistrywillhelpleadusdownnewroadstotreatingdiseaseandhelpingpatients."Robjoinedthecompanyaftercompletinggraduateschoolandapostdoctoralfellowshipfocusingonorganicchemistry."Icameherebecausescienceandinnovationdrivethiscompany.I'mpassionateaboutourmissiontosaveandimprovelives,andIbelievethatmybestdayatwork,thedaymyteammakesapotentiallylife-changingdiscovery,isstillaheadofme,andit'sthereasonthatIstay."InventingforlifeAtMSD,wesayweare.AndRobdefinitelyseeshimselfasaninventor."Chemistshavethisuniqueabilitytocombineatomsandbondsbetweenatomsinauniqueway.Everydaychemistsareinventinghundredsofmoleculesthathaveneverexistedbefore.So,yes,weareinventing,"hesays."Weareinventingtosolveproblems."

  Toexpressourappreciation,MSDbegan#DearCancerHeroes–asocialmediacampaigntorecognizetheirfortitudeandcontributionstothefield.It’sasmallgesturetoshowourgratitude.Wewanttoletclinicaltrialparticipantsknowtheyarenotaloneandthereisawholecommunityofpeoplecheeringthemon.Anyonecanjointhemovementbywritingamessagetocancerclinicaltrialparticipantsonastickynoteandsharingitonsocialmediausing#DearCancerHeroes.Cancerresearchhascomealongwayandstillhasalongwaytogo.However,wewouldn’thavegottentowherewearetodaywithouttheseheroes.Historically,oncologypracticeandclinicaltrialdesignprimarilyfocusedonwherethetumorfirstemerged,suchascolonorrectum,lung,breast,andendometrium.Thisapproachfollowsthelogicofthescalpel:pinpointingthelocationofthetumorfirstenabledsurgicalplans.Morerecently,therehavebeensignificantadvancesinourunderstandingoftheroleofcancerbiomarkersinmolecularandcellularmechanismsthatcandrivetumorgrowth.Biomarkersarebiologicalmolecules(typicallycomprisedofDNA,RNAorprotein)foundintissuesorbloodthatcanserveasasigntobetterunderstandaconditionordisease.Sometimes,thesamebiomarkerisfoundacrossmanydifferenttypesofcancer,regardlessofwherethetumorfirstdeveloped.Withinaspecifictumorlocation,thesebiomarkerscansometimesdifferentiatewhetherthetumorislikelytorespondtoagiventreatment.Assuch,thesebiomarkershavebeenusedtohelpinformclinicalresearch,acceleratingtheprocessofgettingtargetedmedicinestopatientswhereseparatetrialswouldtakeyearstoconduct.Importantly,insomecases,thesefeaturescanbeassessedusinglaboratoryteststhathavelongbeenavailable.Whereatestiseithernotavailable,orforresearchuseonly,thetestmanufacturerpartnerswiththedrugmanufacturertoadvancetogetherintoregulatoryapprovalbygovernmentagencies(suchastheFDA)acompaniondiagnosticassaytoensuresafeandeffectiveuseofthedruginpatientslikelytorespond.Thegoalistouseadeeperunderstandingofthetumorbiologyandassociatedbiomarkerstotackletumorresearchmoreprecisely;goingbeyondsimplywhereatumorarose.Instead,wearelearninghowtoattackacancerbasedonitsbiologyatthecellularlevel.AtMSD,effortsareunderwaytobetterunderstandmicrosatelliteinstability(MSI)andmismatchrepairdeficiency(dMMR).Thesebiomarkersarepresentacrosstumortypes,regardlessoftheoriginallocationofthecancer.ThepresenceofhighlevelsofMSI(MSI-H)ordMMRsignifiesanunderlyingprobleminacell'sabilitytofixerrorsthatoccurwhenDNAreplicates.TumorcellsdeterminedtohaveMSI-HordMMRharborhundredstothousandsofmutations.Theultimateproofofoureffortswillmanifestasanewgenerationofcancermedicines:thosethatfollowthelogicofbiology,notthelogicofthescalpel.Toexpressourappreciation,MSDbegan#DearCancerHeroes–asocialmediacampaigntorecognizetheirfortitudeandcontributionstothefield.It’sasmallgesturetoshowourgratitude.Wewanttoletclinicaltrialparticipantsknowtheyarenotaloneandthereisawholecommunityofpeoplecheeringthemon.Anyonecanjointhemovementbywritingamessagetocancerclinicaltrialparticipantsonastickynoteandsharingitonsocialmediausing#DearCancerHeroes.Cancerresearchhascomealongwayandstillhasalongwaytogo.However,wewouldn’thavegottentowherewearetodaywithouttheseheroes.

  CarolineFox,M.D.ispassionateaboutgenetics.Inmedicalschool,shestudiedtheeffectsoftheenvironmentondiabetesandobesityonatribeofNativeAmericans(certainpopulationsworldwidehaveagreaterpropensitytowardsdiabetes;thistribewasonesuchgroup).Herresearchlefthermotivatedtolearnmoreabouthowgeneticsplaysaroleinmetabolicdiseases.Thatwasmystart,shenotes.Sincethen,almostallofmyresearchhasbeenfocusedonuncoveringthegeneticfoundationsofthesetypesofdiseases.ChangingPerceptionsPriortojoiningMSDResearchLaboratoriesinBoston,CarolineworkedattheNationalInstitutesofHealth.There,sheledalabthatstudiedmetabolicriskfactorsforcardiovasculardiseaseaspartofthe,apioneeringlong-termpopulationstudyofcardiovasculardisease.But,shenotes,theshifttoMSDwasarelativelyeasyone.IwasimpressedbyMSDseffortstoleveragehumangeneticstodrivedrugdiscovery,shesays.Forme,itwastheperfectnextstepfromtheworkthatIhadbeendoinginacademia.Genetics:TheNewFrontierWe'relucky—CarolinespassionforgeneticsisagreatfitforMSD.Inourlabsandacrosstheindustry,weareseeinganincreaseduseofhumangeneticstohelpdeterminewhetherpatientswillrespondtoacertaindrugornot,ShepointstoMSD'sactiveresearchcollaborationswithscientistsaroundtheworldaimedatadvancingthisfieldofscience.Iamveryenthusiasticaboutwhereourresearchmaylead.CarolineFox,M.D.ispassionateaboutgenetics.Inmedicalschool,shestudiedtheeffectsoftheenvironmentondiabetesandobesityonatribeofNativeAmericans(certainpopulationsworldwidehaveagreaterpropensitytowardsdiabetes;thistribewasonesuchgroup).Herresearchlefthermotivatedtolearnmoreabouthowgeneticsplaysaroleinmetabolicdiseases.Thatwasmystart,shenotes.Sincethen,almostallofmyresearchhasbeenfocusedonuncoveringthegeneticfoundationsofthesetypesofdiseases.ChangingPerceptionsPriortojoiningMSDResearchLaboratoriesinBoston,CarolineworkedattheNationalInstitutesofHealth.There,sheledalabthatstudiedmetabolicriskfactorsforcardiovasculardiseaseaspartofthe,apioneeringlong-termpopulationstudyofcardiovasculardisease.But,shenotes,theshifttoMSDwasarelativelyeasyone.IwasimpressedbyMSDseffortstoleveragehumangeneticstodrivedrugdiscovery,shesays.Forme,itwastheperfectnextstepfromtheworkthatIhadbeendoinginacademia.Genetics:TheNewFrontierWe'relucky—CarolinespassionforgeneticsisagreatfitforMSD.Inourlabsandacrosstheindustry,weareseeinganincreaseduseofhumangeneticstohelpdeterminewhetherpatientswillrespondtoacertaindrugornot,ShepointstoMSD'sactiveresearchcollaborationswithscientistsaroundtheworldaimedatadvancingthisfieldofscience.Iamveryenthusiasticaboutwhereourresearchmaylead.CarolineFox,M.D.ispassionateaboutgenetics.Inmedicalschool,shestudiedtheeffectsoftheenvironmentondiabetesandobesityonatribeofNativeAmericans(certainpopulationsworldwidehaveagreaterpropensitytowardsdiabetes;thistribewasonesuchgroup).Herresearchlefthermotivatedtolearnmoreabouthowgeneticsplaysaroleinmetabolicdiseases.Thatwasmystart,shenotes.Sincethen,almostallofmyresearchhasbeenfocusedonuncoveringthegeneticfoundationsofthesetypesofdiseases.ChangingPerceptionsPriortojoiningMSDResearchLaboratoriesinBoston,CarolineworkedattheNationalInstitutesofHealth.There,sheledalabthatstudiedmetabolicriskfactorsforcardiovasculardiseaseaspartofthe,apioneeringlong-termpopulationstudyofcardiovasculardisease.But,shenotes,theshifttoMSDwasarelativelyeasyone.IwasimpressedbyMSDseffortstoleveragehumangeneticstodrivedrugdiscovery,shesays.Forme,itwastheperfectnextstepfromtheworkthatIhadbeendoinginacademia.Genetics:TheNewFrontierWe'relucky—CarolinespassionforgeneticsisagreatfitforMSD.Inourlabsandacrosstheindustry,weareseeinganincreaseduseofhumangeneticstohelpdeterminewhetherpatientswillrespondtoacertaindrugornot,ShepointstoMSD'sactiveresearchcollaborationswithscientistsaroundtheworldaimedatadvancingthisfieldofscience.Iamveryenthusiasticaboutwhereourresearchmaylead.

  Jameslikeslogicpuzzles.Andwordproblems.Luckily,hegetstoapplytheseinterestsinhisworkeveryday.Jamesisacomputationalchemist–heworkswithMSD’schemistryteams,applyingpredictivemodellingtoidentifywaystodesigndrugsandanalyzedatatohelpourscientistsprioritizethenextcompoundstomakeandtest.Althoughthesearecomplexproblemsandcomplexquestionsthatwe’retryingtosolve,wetakelogicalsteps,explainsJames.Foreveryquestion,there’sreallyananswer,yousometimesjusthavetospendalittlebitmoretimethinkingaboutit,andtakeastepbackandlookatwhat’sactuallyinfrontofyou.Bettermolecules,fasterInourgroup’sroleindrugdiscovery,wehavethismantraof‘bettermolecules,faster,saysJames.Ifachemisthas100compoundsthatshe’sthinkingaboutmaking,computationally,wecanhelpprioritizewhichonestostartwithbasedonrationaldrugdesign.Jamesenjoysbeingpartofateamworkingtoachieveasingulargoal:tocreatemedicinesthatwillhelpthepeoplewhoneedthem.And,hebelievesthatcollaborationisveryimportantforresearchanddevelopment:Youcan'tdoaprojectonyourown;youneedotherstoassistandhelp,notjustbycontributingintheirindividualrole,butalsowiththeirthinking.Jamesandhiscolleagueshavealotofexperiencewithperseveranceanddetermination,too.Ourteamsofscientistsdesign,developandscreenthousandsofcompoundsandantibodiestoultimatelyadvanceonlyafewofthemostpromisingleadcandidatesintoclinicaltesting.Moleculardesignanddevelopmentisaniterativeprocess.Youhavetostickwithit.It'scontinuouslymakingmodificationsandadaptingandevolving,eventuallygettingdowntheroadorthepipelinetomakeadrug…that'swhat'sexcitingaboutit.It’sallaboutthepatientsEveryday,IcometoworkknowingthatI’mworkingtomakeadrug.And,Idon'tknowiftodayI’mgoingtoopenupanemailwithresultssaying,‘we'veaccomplishedthisor‘weneedtochangethat.’Butregardlessofwhatthoseresultsare,it'sgoingtobeprogresstogettothatendpoint.”Jameslikeslogicpuzzles.Andwordproblems.Luckily,hegetstoapplytheseinterestsinhisworkeveryday.Jamesisacomputationalchemist–heworkswithMSD’schemistryteams,applyingpredictivemodellingtoidentifywaystodesigndrugsandanalyzedatatohelpourscientistsprioritizethenextcompoundstomakeandtest.Althoughthesearecomplexproblemsandcomplexquestionsthatwe’retryingtosolve,wetakelogicalsteps,explainsJames.Foreveryquestion,there’sreallyananswer,yousometimesjusthavetospendalittlebitmoretimethinkingaboutit,andtakeastepbackandlookatwhat’sactuallyinfrontofyou.Bettermolecules,fasterInourgroup’sroleindrugdiscovery,wehavethismantraof‘bettermolecules,faster,saysJames.Ifachemisthas100compoundsthatshe’sthinkingaboutmaking,computationally,wecanhelpprioritizewhichonestostartwithbasedonrationaldrugdesign.Jamesenjoysbeingpartofateamworkingtoachieveasingulargoal:tocreatemedicinesthatwillhelpthepeoplewhoneedthem.And,hebelievesthatcollaborationisveryimportantforresearchanddevelopment:Youcan'tdoaprojectonyourown;youneedotherstoassistandhelp,notjustbycontributingintheirindividualrole,butalsowiththeirthinking.Jamesandhiscolleagueshavealotofexperiencewithperseveranceanddetermination,too.Ourteamsofscientistsdesign,developandscreenthousandsofcompoundsandantibodiestoultimatelyadvanceonlyafewofthemostpromisingleadcandidatesintoclinicaltesting.Moleculardesignanddevelopmentisaniterativeprocess.Youhavetostickwithit.It'scontinuouslymakingmodificationsandadaptingandevolving,eventuallygettingdowntheroadorthepipelinetomakeadrug…that'swhat'sexcitingaboutit.It’sallaboutthepatientsEveryday,IcometoworkknowingthatI’mworkingtomakeadrug.And,Idon'tknowiftodayI’mgoingtoopenupanemailwithresultssaying,‘we'veaccomplishedthisor‘weneedtochangethat.’Butregardlessofwhatthoseresultsare,it'sgoingtobeprogresstogettothatendpoint.”CarolineFox,M.D.ispassionateaboutgenetics.Inmedicalschool,shestudiedtheeffectsoftheenvironmentondiabetesandobesityonatribeofNativeAmericans(certainpopulationsworldwidehaveagreaterpropensitytowardsdiabetes;thistribewasonesuchgroup).Herresearchlefthermotivatedtolearnmoreabouthowgeneticsplaysaroleinmetabolicdiseases.Thatwasmystart,shenotes.Sincethen,almostallofmyresearchhasbeenfocusedonuncoveringthegeneticfoundationsofthesetypesofdiseases.ChangingPerceptionsPriortojoiningMSDResearchLaboratoriesinBoston,CarolineworkedattheNationalInstitutesofHealth.There,sheledalabthatstudiedmetabolicriskfactorsforcardiovasculardiseaseaspartofthe,apioneeringlong-termpopulationstudyofcardiovasculardisease.But,shenotes,theshifttoMSDwasarelativelyeasyone.IwasimpressedbyMSDseffortstoleveragehumangeneticstodrivedrugdiscovery,shesays.Forme,itwastheperfectnextstepfromtheworkthatIhadbeendoinginacademia.Genetics:TheNewFrontierWe'relucky—CarolinespassionforgeneticsisagreatfitforMSD.Inourlabsandacrosstheindustry,weareseeinganincreaseduseofhumangeneticstohelpdeterminewhetherpatientswillrespondtoacertaindrugornot,ShepointstoMSD'sactiveresearchcollaborationswithscientistsaroundtheworldaimedatadvancingthisfieldofscience.Iamveryenthusiasticaboutwhereourresearchmaylead.

  Toexpressourappreciation,MSDbegan#DearCancerHeroes–asocialmediacampaigntorecognizetheirfortitudeandcontributionstothefield.It’sasmallgesturetoshowourgratitude.Wewanttoletclinicaltrialparticipantsknowtheyarenotaloneandthereisawholecommunityofpeoplecheeringthemon.Anyonecanjointhemovementbywritingamessagetocancerclinicaltrialparticipantsonastickynoteandsharingitonsocialmediausing#DearCancerHeroes.Cancerresearchhascomealongwayandstillhasalongwaytogo.However,wewouldn’thavegottentowherewearetodaywithouttheseheroes.Toexpressourappreciation,MSDbegan#DearCancerHeroes–asocialmediacampaigntorecognizetheirfortitudeandcontributionstothefield.It’sasmallgesturetoshowourgratitude.Wewanttoletclinicaltrialparticipantsknowtheyarenotaloneandthereisawholecommunityofpeoplecheeringthemon.Anyonecanjointhemovementbywritingamessagetocancerclinicaltrialparticipantsonastickynoteandsharingitonsocialmediausing#DearCancerHeroes.Cancerresearchhascomealongwayandstillhasalongwaytogo.However,wewouldn’thavegottentowherewearetodaywithouttheseheroes.“MyuncleIvanwasaseverediabetespatient—heneededinjectionsthreetimesaday.Hewaswithoutinsulinformorethanamonth.EvenIwasnotaware,”Pablorecounts.“Whenhefinallyreceivedinsulin,hewasinbadcondition.Severalweekslater,hishealthdeclined,hehadrenalfailure,andhedied.”ThedroneteamrecentlyacknowledgedPablo’scontributions,andhispersonalloss,bygivingtheprojectanewnickname.Oncecalled“MajorTom”aftertheDavidBowiesong,it’snow“ProjectIvan.”“Idon’thavewordsenoughtoshowmygratitude,”Pablosays.“Thisisaboutsavinglives.”

  Ourcompanyiscommittedtodiscoveringsmart,sustainablewaystoexpandaccesstohealthcare,especiallyinareaswithlimitedinfrastructureandresources.Giventhesignificanceofthischallenge,itisonlybyworkinginpartnershipwithothers—governments,donors,patientorganizations,healthcareprofessionals,NGOs,academicinstitutions,multilateralorganizationsandtheprivatesector—thatwecanwemakethestrongestcontribution.TheMSDFellowshipforGlobalHealthisbuiltonthenotionofpartneringtostrengthenthecapacityandreachofnonprofitorganizationswhich,inturn,willultimatelysolvesomeoftheworld’sgreatesthealthcarechallenges.CarolineFox,M.D.ispassionateaboutgenetics.Inmedicalschool,shestudiedtheeffectsoftheenvironmentondiabetesandobesityonatribeofNativeAmericans(certainpopulationsworldwidehaveagreaterpropensitytowardsdiabetes;thistribewasonesuchgroup).Herresearchlefthermotivatedtolearnmoreabouthowgeneticsplaysaroleinmetabolicdiseases.Thatwasmystart,shenotes.Sincethen,almostallofmyresearchhasbeenfocusedonuncoveringthegeneticfoundationsofthesetypesofdiseases.ChangingPerceptionsPriortojoiningMSDResearchLaboratoriesinBoston,CarolineworkedattheNationalInstitutesofHealth.There,sheledalabthatstudiedmetabolicriskfactorsforcardiovasculardiseaseaspartofthe,apioneeringlong-termpopulationstudyofcardiovasculardisease.But,shenotes,theshifttoMSDwasarelativelyeasyone.IwasimpressedbyMSDseffortstoleveragehumangeneticstodrivedrugdiscovery,shesays.Forme,itwastheperfectnextstepfromtheworkthatIhadbeendoinginacademia.Genetics:TheNewFrontierWe'relucky—CarolinespassionforgeneticsisagreatfitforMSD.Inourlabsandacrosstheindustry,weareseeinganincreaseduseofhumangeneticstohelpdeterminewhetherpatientswillrespondtoacertaindrugornot,ShepointstoMSD'sactiveresearchcollaborationswithscientistsaroundtheworldaimedatadvancingthisfieldofscience.Iamveryenthusiasticaboutwhereourresearchmaylead.Historically,oncologypracticeandclinicaltrialdesignprimarilyfocusedonwherethetumorfirstemerged,suchascolonorrectum,lung,breast,andendometrium.Thisapproachfollowsthelogicofthescalpel:pinpointingthelocationofthetumorfirstenabledsurgicalplans.Morerecently,therehavebeensignificantadvancesinourunderstandingoftheroleofcancerbiomarkersinmolecularandcellularmechanismsthatcandrivetumorgrowth.Biomarkersarebiologicalmolecules(typicallycomprisedofDNA,RNAorprotein)foundintissuesorbloodthatcanserveasasigntobetterunderstandaconditionordisease.Sometimes,thesamebiomarkerisfoundacrossmanydifferenttypesofcancer,regardlessofwherethetumorfirstdeveloped.Withinaspecifictumorlocation,thesebiomarkerscansometimesdifferentiatewhetherthetumorislikelytorespondtoagiventreatment.Assuch,thesebiomarkershavebeenusedtohelpinformclinicalresearch,acceleratingtheprocessofgettingtargetedmedicinestopatientswhereseparatetrialswouldtakeyearstoconduct.Importantly,insomecases,thesefeaturescanbeassessedusinglaboratoryteststhathavelongbeenavailable.Whereatestiseithernotavailable,orforresearchuseonly,thetestmanufacturerpartnerswiththedrugmanufacturertoadvancetogetherintoregulatoryapprovalbygovernmentagencies(suchastheFDA)acompaniondiagnosticassaytoensuresafeandeffectiveuseofthedruginpatientslikelytorespond.Thegoalistouseadeeperunderstandingofthetumorbiologyandassociatedbiomarkerstotackletumorresearchmoreprecisely;goingbeyondsimplywhereatumorarose.Instead,wearelearninghowtoattackacancerbasedonitsbiologyatthecellularlevel.AtMSD,effortsareunderwaytobetterunderstandmicrosatelliteinstability(MSI)andmismatchrepairdeficiency(dMMR).Thesebiomarkersarepresentacrosstumortypes,regardlessoftheoriginallocationofthecancer.ThepresenceofhighlevelsofMSI(MSI-H)ordMMRsignifiesanunderlyingprobleminacell'sabilitytofixerrorsthatoccurwhenDNAreplicates.TumorcellsdeterminedtohaveMSI-HordMMRharborhundredstothousandsofmutations.Theultimateproofofoureffortswillmanifestasanewgenerationofcancermedicines:thosethatfollowthelogicofbiology,notthelogicofthescalpel.

  Dr.Chenghasbeentreatingheadandneckcancerpatientsformanyyears.Thisishispersonalperspective.Ihavetreatedpatientswithheadandneckcancersformanyyears,soIhaveseen,upclose,thedifficultexperienceoflivingwithheadandneckcancer.Cancerisatryingsituationforallpatientsandtheirlovedones,butheadandneckpatientsfacecancerinauniqueanddifficultway,withtheirdiseaseandtumorsoftenvisibletothepublic.Ihavebeeninvolvedinresearchforyearsaspartofscientists'decades-longendeavortobringforwardmeaningfuladvancesforpatientsdiagnosedwiththispotentiallyaggressivedisease.Untilrecently,suchadvanceswerehardtocomebyandmypatientsandIstruggledwiththelimitedtreatmentoptionsavailable.Butwhilethereisasignificantneedfornewtreatmentoptions,thegoodnewsisthattherehavebeensomeimprovementsinsurvivalratesovertheyearsandweareseeinganewandencouragingfutureahead.Wehavebeguntoleverageourunderstandingofbiologytodevelopmoreprecisetherapies.AtMSD,wearefocusedonimmuno-oncologyresearch,whichstudiestheroleoftheimmunesystemindetectingandfightingcancer.Wearestudyingthepotentialofthisapproach,whichaimstoharnessandrestorethebodysabilitytodetectandfightcancercells,inanumberofcancers,includingheadandneckcancer.Immuno-oncologyhasalreadysignificantlychangedthewaycertaincancersaretreated,includingmelanomaandlungcancer,aswellasinthetreatmentofheadandneckcancer.Changeiscomingtotheheadandneckcancerlandscape–anditisthrillingtobeapartofit.TobeabletoseehowourresearchandeffortsatMSDarehavingadirectimpactonhowphysiciansapproachthetreatmentoftheirpatientsandwhatpatientsmayexpectfromtheirtreatmentiswhatmotivatesustoworkharder.Chemistryhasbeencentraltoourbusinessofsinceourearliestdaysasacompany.Historically,ourdrugdiscoveryprocessprimarilycenteredaroundsmallmolecules.Then,thebirthofbiotechnologyinthelate1970s/early1980saddedbiologics,orengineeredproteins,tothemix.Today,newmodalitiesareemergingthatshowastrongpotentialtotargetcomplexdiseasesthathavenotyetbeenreachablewitheithersmallmoleculesorbiologics.RobGarbaccioisleadingatalentedteamofchemistswhoarehelpingguideMSD’sentryintothisexcitingnewfieldofmedicine.IntroducinganddiscoveringnewwaysforwardRobistheassociatevicepresident,ChemistryCapabilitiesforAcceleratingTherapeutics(CCAT),adiscoverychemistryteamthatislookingathowtogobeyondthetraditionalmethodsofdiscoveringanddevelopingmedicines."Therearecertaindiseasetargetsthatarereallyhardto'reach'andimpactusingtraditionalmethods,"henotes."SopartofthegroupIoverseetriestofigureouthowwecanemploynewermodalities,suchaspeptides,bioconjugates,andoligonucleotides,toaddressthechallengingtargetsthatareincreasinglyemergingfrombiologicalresearch."Rob'sgroupisnotfocusedonanyspecifictherapeuticarea--theyareseekingnewwaystoaddressthemostdifficultdiseasetargets."Inoncology,infectiousdiseases,andneuroscience,forexample,we’relookingforthosetargetsthatourcolleaguessay,'Ifonlywecouldmodulatethistarget,webelievewemightbeabletopotentiallyinterruptthediseaseprocessandhelppatients,'"henotes.Using‘creativechemistry’totreatdiseaseIt'scomplexwork,tobesure,butthat'swhatmakesitsointriguingandinspiringforRobandhisteam."ThethingthatIlikethemostaboutmyworkisthebeliefthattheremaybeapathforwardforthetreatmentofeachandeveryoneofthesediseases.Wejustcan'tseeityetbecausethebiologyissocomplex,"saysRob."Asresearcherscontinuetoimproveourunderstandingofdiseasebiology,Ibelievethatcombiningthatknowledgewithcreativechemistrywillhelpleadusdownnewroadstotreatingdiseaseandhelpingpatients."Robjoinedthecompanyaftercompletinggraduateschoolandapostdoctoralfellowshipfocusingonorganicchemistry."Icameherebecausescienceandinnovationdrivethiscompany.I'mpassionateaboutourmissiontosaveandimprovelives,andIbelievethatmybestdayatwork,thedaymyteammakesapotentiallylife-changingdiscovery,isstillaheadofme,andit'sthereasonthatIstay."InventingforlifeAtMSD,wesayweare.AndRobdefinitelyseeshimselfasaninventor."Chemistshavethisuniqueabilitytocombineatomsandbondsbetweenatomsinauniqueway.Everydaychemistsareinventinghundredsofmoleculesthathaveneverexistedbefore.So,yes,weareinventing,"hesays."Weareinventingtosolveproblems."Ourcompanyiscommittedtodiscoveringsmart,sustainablewaystoexpandaccesstohealthcare,especiallyinareaswithlimitedinfrastructureandresources.Giventhesignificanceofthischallenge,itisonlybyworkinginpartnershipwithothers—governments,donors,patientorganizations,healthcareprofessionals,NGOs,academicinstitutions,multilateralorganizationsandtheprivatesector—thatwecanwemakethestrongestcontribution.TheMSDFellowshipforGlobalHealthisbuiltonthenotionofpartneringtostrengthenthecapacityandreachofnonprofitorganizationswhich,inturn,willultimatelysolvesomeoftheworld’sgreatesthealthcarechallenges.

  Toexpressourappreciation,MSDbegan#DearCancerHeroes–asocialmediacampaigntorecognizetheirfortitudeandcontributionstothefield.It’sasmallgesturetoshowourgratitude.Wewanttoletclinicaltrialparticipantsknowtheyarenotaloneandthereisawholecommunityofpeoplecheeringthemon.Anyonecanjointhemovementbywritingamessagetocancerclinicaltrialparticipantsonastickynoteandsharingitonsocialmediausing#DearCancerHeroes.Cancerresearchhascomealongwayandstillhasalongwaytogo.However,wewouldn’thavegottentowherewearetodaywithouttheseheroes.Chemistryhasbeencentraltoourbusinessofsinceourearliestdaysasacompany.Historically,ourdrugdiscoveryprocessprimarilycenteredaroundsmallmolecules.Then,thebirthofbiotechnologyinthelate1970s/early1980saddedbiologics,orengineeredproteins,tothemix.Today,newmodalitiesareemergingthatshowastrongpotentialtotargetcomplexdiseasesthathavenotyetbeenreachablewitheithersmallmoleculesorbiologics.RobGarbaccioisleadingatalentedteamofchemistswhoarehelpingguideMSD’sentryintothisexcitingnewfieldofmedicine.IntroducinganddiscoveringnewwaysforwardRobistheassociatevicepresident,ChemistryCapabilitiesforAcceleratingTherapeutics(CCAT),adiscoverychemistryteamthatislookingathowtogobeyondthetraditionalmethodsofdiscoveringanddevelopingmedicines."Therearecertaindiseasetargetsthatarereallyhardto'reach'andimpactusingtraditionalmethods,"henotes."SopartofthegroupIoverseetriestofigureouthowwecanemploynewermodalities,suchaspeptides,bioconjugates,andoligonucleotides,toaddressthechallengingtargetsthatareincreasinglyemergingfrombiologicalresearch."Rob'sgroupisnotfocusedonanyspecifictherapeuticarea--theyareseekingnewwaystoaddressthemostdifficultdiseasetargets."Inoncology,infectiousdiseases,andneuroscience,forexample,we’relookingforthosetargetsthatourcolleaguessay,'Ifonlywecouldmodulatethistarget,webelievewemightbeabletopotentiallyinterruptthediseaseprocessandhelppatients,'"henotes.Using‘creativechemistry’totreatdiseaseIt'scomplexwork,tobesure,butthat'swhatmakesitsointriguingandinspiringforRobandhisteam."ThethingthatIlikethemostaboutmyworkisthebeliefthattheremaybeapathforwardforthetreatmentofeachandeveryoneofthesediseases.Wejustcan'tseeityetbecausethebiologyissocomplex,"saysRob."Asresearcherscontinuetoimproveourunderstandingofdiseasebiology,Ibelievethatcombiningthatknowledgewithcreativechemistrywillhelpleadusdownnewroadstotreatingdiseaseandhelpingpatients."Robjoinedthecompanyaftercompletinggraduateschoolandapostdoctoralfellowshipfocusingonorganicchemistry."Icameherebecausescienceandinnovationdrivethiscompany.I'mpassionateaboutourmissiontosaveandimprovelives,andIbelievethatmybestdayatwork,thedaymyteammakesapotentiallylife-changingdiscovery,isstillaheadofme,andit'sthereasonthatIstay."InventingforlifeAtMSD,wesayweare.AndRobdefinitelyseeshimselfasaninventor."Chemistshavethisuniqueabilitytocombineatomsandbondsbetweenatomsinauniqueway.Everydaychemistsareinventinghundredsofmoleculesthathaveneverexistedbefore.So,yes,weareinventing,"hesays."Weareinventingtosolveproblems."Dr.Chenghasbeentreatingheadandneckcancerpatientsformanyyears.Thisishispersonalperspective.Ihavetreatedpatientswithheadandneckcancersformanyyears,soIhaveseen,upclose,thedifficultexperienceoflivingwithheadandneckcancer.Cancerisatryingsituationforallpatientsandtheirlovedones,butheadandneckpatientsfacecancerinauniqueanddifficultway,withtheirdiseaseandtumorsoftenvisibletothepublic.Ihavebeeninvolvedinresearchforyearsaspartofscientists'decades-longendeavortobringforwardmeaningfuladvancesforpatientsdiagnosedwiththispotentiallyaggressivedisease.Untilrecently,suchadvanceswerehardtocomebyandmypatientsandIstruggledwiththelimitedtreatmentoptionsavailable.Butwhilethereisasignificantneedfornewtreatmentoptions,thegoodnewsisthattherehavebeensomeimprovementsinsurvivalratesovertheyearsandweareseeinganewandencouragingfutureahead.Wehavebeguntoleverageourunderstandingofbiologytodevelopmoreprecisetherapies.AtMSD,wearefocusedonimmuno-oncologyresearch,whichstudiestheroleoftheimmunesystemindetectingandfightingcancer.Wearestudyingthepotentialofthisapproach,whichaimstoharnessandrestorethebodysabilitytodetectandfightcancercells,inanumberofcancers,includingheadandneckcancer.Immuno-oncologyhasalreadysignificantlychangedthewaycertaincancersaretreated,includingmelanomaandlungcancer,aswellasinthetreatmentofheadandneckcancer.Changeiscomingtotheheadandneckcancerlandscape–anditisthrillingtobeapartofit.TobeabletoseehowourresearchandeffortsatMSDarehavingadirectimpactonhowphysiciansapproachthetreatmentoftheirpatientsandwhatpatientsmayexpectfromtheirtreatmentiswhatmotivatesustoworkharder.

  Jameslikeslogicpuzzles.Andwordproblems.Luckily,hegetstoapplytheseinterestsinhisworkeveryday.Jamesisacomputationalchemist–heworkswithMSD’schemistryteams,applyingpredictivemodellingtoidentifywaystodesigndrugsandanalyzedatatohelpourscientistsprioritizethenextcompoundstomakeandtest.Althoughthesearecomplexproblemsandcomplexquestionsthatwe’retryingtosolve,wetakelogicalsteps,explainsJames.Foreveryquestion,there’sreallyananswer,yousometimesjusthavetospendalittlebitmoretimethinkingaboutit,andtakeastepbackandlookatwhat’sactuallyinfrontofyou.Bettermolecules,fasterInourgroup’sroleindrugdiscovery,wehavethismantraof‘bettermolecules,faster,saysJames.Ifachemisthas100compoundsthatshe’sthinkingaboutmaking,computationally,wecanhelpprioritizewhichonestostartwithbasedonrationaldrugdesign.Jamesenjoysbeingpartofateamworkingtoachieveasingulargoal:tocreatemedicinesthatwillhelpthepeoplewhoneedthem.And,hebelievesthatcollaborationisveryimportantforresearchanddevelopment:Youcan'tdoaprojectonyourown;youneedotherstoassistandhelp,notjustbycontributingintheirindividualrole,butalsowiththeirthinking.Jamesandhiscolleagueshavealotofexperiencewithperseveranceanddetermination,too.Ourteamsofscientistsdesign,developandscreenthousandsofcompoundsandantibodiestoultimatelyadvanceonlyafewofthemostpromisingleadcandidatesintoclinicaltesting.Moleculardesignanddevelopmentisaniterativeprocess.Youhavetostickwithit.It'scontinuouslymakingmodificationsandadaptingandevolving,eventuallygettingdowntheroadorthepipelinetomakeadrug…that'swhat'sexcitingaboutit.It’sallaboutthepatientsEveryday,IcometoworkknowingthatI’mworkingtomakeadrug.And,Idon'tknowiftodayI’mgoingtoopenupanemailwithresultssaying,‘we'veaccomplishedthisor‘weneedtochangethat.’Butregardlessofwhatthoseresultsare,it'sgoingtobeprogresstogettothatendpoint.”Toexpressourappreciation,MSDbegan#DearCancerHeroes–asocialmediacampaigntorecognizetheirfortitudeandcontributionstothefield.It’sasmallgesturetoshowourgratitude.Wewanttoletclinicaltrialparticipantsknowtheyarenotaloneandthereisawholecommunityofpeoplecheeringthemon.Anyonecanjointhemovementbywritingamessagetocancerclinicaltrialparticipantsonastickynoteandsharingitonsocialmediausing#DearCancerHeroes.Cancerresearchhascomealongwayandstillhasalongwaytogo.However,wewouldn’thavegottentowherewearetodaywithouttheseheroes.Dr.Chenghasbeentreatingheadandneckcancerpatientsformanyyears.Thisishispersonalperspective.Ihavetreatedpatientswithheadandneckcancersformanyyears,soIhaveseen,upclose,thedifficultexperienceoflivingwithheadandneckcancer.Cancerisatryingsituationforallpatientsandtheirlovedones,butheadandneckpatientsfacecancerinauniqueanddifficultway,withtheirdiseaseandtumorsoftenvisibletothepublic.Ihavebeeninvolvedinresearchforyearsaspartofscientists'decades-longendeavortobringforwardmeaningfuladvancesforpatientsdiagnosedwiththispotentiallyaggressivedisease.Untilrecently,suchadvanceswerehardtocomebyandmypatientsandIstruggledwiththelimitedtreatmentoptionsavailable.Butwhilethereisasignificantneedfornewtreatmentoptions,thegoodnewsisthattherehavebeensomeimprovementsinsurvivalratesovertheyearsandweareseeinganewandencouragingfutureahead.Wehavebeguntoleverageourunderstandingofbiologytodevelopmoreprecisetherapies.AtMSD,wearefocusedonimmuno-oncologyresearch,whichstudiestheroleoftheimmunesystemindetectingandfightingcancer.Wearestudyingthepotentialofthisapproach,whichaimstoharnessandrestorethebodysabilitytodetectandfightcancercells,inanumberofcancers,includingheadandneckcancer.Immuno-oncologyhasalreadysignificantlychangedthewaycertaincancersaretreated,includingmelanomaandlungcancer,aswellasinthetreatmentofheadandneckcancer.Changeiscomingtotheheadandneckcancerlandscape–anditisthrillingtobeapartofit.TobeabletoseehowourresearchandeffortsatMSDarehavingadirectimpactonhowphysiciansapproachthetreatmentoftheirpatientsandwhatpatientsmayexpectfromtheirtreatmentiswhatmotivatesustoworkharder.

  Jameslikeslogicpuzzles.Andwordproblems.Luckily,hegetstoapplytheseinterestsinhisworkeveryday.Jamesisacomputationalchemist–heworkswithMSD’schemistryteams,applyingpredictivemodellingtoidentifywaystodesigndrugsandanalyzedatatohelpourscientistsprioritizethenextcompoundstomakeandtest.Althoughthesearecomplexproblemsandcomplexquestionsthatwe’retryingtosolve,wetakelogicalsteps,explainsJames.Foreveryquestion,there’sreallyananswer,yousometimesjusthavetospendalittlebitmoretimethinkingaboutit,andtakeastepbackandlookatwhat’sactuallyinfrontofyou.Bettermolecules,fasterInourgroup’sroleindrugdiscovery,wehavethismantraof‘bettermolecules,faster,saysJames.Ifachemisthas100compoundsthatshe’sthinkingaboutmaking,computationally,wecanhelpprioritizewhichonestostartwithbasedonrationaldrugdesign.Jamesenjoysbeingpartofateamworkingtoachieveasingulargoal:tocreatemedicinesthatwillhelpthepeoplewhoneedthem.And,hebelievesthatcollaborationisveryimportantforresearchanddevelopment:Youcan'tdoaprojectonyourown;youneedotherstoassistandhelp,notjustbycontributingintheirindividualrole,butalsowiththeirthinking.Jamesandhiscolleagueshavealotofexperiencewithperseveranceanddetermination,too.Ourteamsofscientistsdesign,developandscreenthousandsofcompoundsandantibodiestoultimatelyadvanceonlyafewofthemostpromisingleadcandidatesintoclinicaltesting.Moleculardesignanddevelopmentisaniterativeprocess.Youhavetostickwithit.It'scontinuouslymakingmodificationsandadaptingandevolving,eventuallygettingdowntheroadorthepipelinetomakeadrug…that'swhat'sexcitingaboutit.It’sallaboutthepatientsEveryday,IcometoworkknowingthatI’mworkingtomakeadrug.And,Idon'tknowiftodayI’mgoingtoopenupanemailwithresultssaying,‘we'veaccomplishedthisor‘weneedtochangethat.’Butregardlessofwhatthoseresultsare,it'sgoingtobeprogresstogettothatendpoint.”Toexpressourappreciation,MSDbegan#DearCancerHeroes–asocialmediacampaigntorecognizetheirfortitudeandcontributionstothefield.It’sasmallgesturetoshowourgratitude.Wewanttoletclinicaltrialparticipantsknowtheyarenotaloneandthereisawholecommunityofpeoplecheeringthemon.Anyonecanjointhemovementbywritingamessagetocancerclinicaltrialparticipantsonastickynoteandsharingitonsocialmediausing#DearCancerHeroes.Cancerresearchhascomealongwayandstillhasalongwaytogo.However,wewouldn’thavegottentowherewearetodaywithouttheseheroes.Chemistryhasbeencentraltoourbusinessofsinceourearliestdaysasacompany.Historically,ourdrugdiscoveryprocessprimarilycenteredaroundsmallmolecules.Then,thebirthofbiotechnologyinthelate1970s/early1980saddedbiologics,orengineeredproteins,tothemix.Today,newmodalitiesareemergingthatshowastrongpotentialtotargetcomplexdiseasesthathavenotyetbeenreachablewitheithersmallmoleculesorbiologics.RobGarbaccioisleadingatalentedteamofchemistswhoarehelpingguideMSD’sentryintothisexcitingnewfieldofmedicine.IntroducinganddiscoveringnewwaysforwardRobistheassociatevicepresident,ChemistryCapabilitiesforAcceleratingTherapeutics(CCAT),adiscoverychemistryteamthatislookingathowtogobeyondthetraditionalmethodsofdiscoveringanddevelopingmedicines."Therearecertaindiseasetargetsthatarereallyhardto'reach'andimpactusingtraditionalmethods,"henotes."SopartofthegroupIoverseetriestofigureouthowwecanemploynewermodalities,suchaspeptides,bioconjugates,andoligonucleotides,toaddressthechallengingtargetsthatareincreasinglyemergingfrombiologicalresearch."Rob'sgroupisnotfocusedonanyspecifictherapeuticarea--theyareseekingnewwaystoaddressthemostdifficultdiseasetargets."Inoncology,infectiousdiseases,andneuroscience,forexample,we’relookingforthosetargetsthatourcolleaguessay,'Ifonlywecouldmodulatethistarget,webelievewemightbeabletopotentiallyinterruptthediseaseprocessandhelppatients,'"henotes.Using‘creativechemistry’totreatdiseaseIt'scomplexwork,tobesure,butthat'swhatmakesitsointriguingandinspiringforRobandhisteam."ThethingthatIlikethemostaboutmyworkisthebeliefthattheremaybeapathforwardforthetreatmentofeachandeveryoneofthesediseases.Wejustcan'tseeityetbecausethebiologyissocomplex,"saysRob."Asresearcherscontinuetoimproveourunderstandingofdiseasebiology,Ibelievethatcombiningthatknowledgewithcreativechemistrywillhelpleadusdownnewroadstotreatingdiseaseandhelpingpatients."Robjoinedthecompanyaftercompletinggraduateschoolandapostdoctoralfellowshipfocusingonorganicchemistry."Icameherebecausescienceandinnovationdrivethiscompany.I'mpassionateaboutourmissiontosaveandimprovelives,andIbelievethatmybestdayatwork,thedaymyteammakesapotentiallylife-changingdiscovery,isstillaheadofme,andit'sthereasonthatIstay."InventingforlifeAtMSD,wesayweare.AndRobdefinitelyseeshimselfasaninventor."Chemistshavethisuniqueabilitytocombineatomsandbondsbetweenatomsinauniqueway.Everydaychemistsareinventinghundredsofmoleculesthathaveneverexistedbefore.So,yes,weareinventing,"hesays."Weareinventingtosolveproblems."

  CarolineFox,M.D.ispassionateaboutgenetics.Inmedicalschool,shestudiedtheeffectsoftheenvironmentondiabetesandobesityonatribeofNativeAmericans(certainpopulationsworldwidehaveagreaterpropensitytowardsdiabetes;thistribewasonesuchgroup).Herresearchlefthermotivatedtolearnmoreabouthowgeneticsplaysaroleinmetabolicdiseases.Thatwasmystart,shenotes.Sincethen,almostallofmyresearchhasbeenfocusedonuncoveringthegeneticfoundationsofthesetypesofdiseases.ChangingPerceptionsPriortojoiningMSDResearchLaboratoriesinBoston,CarolineworkedattheNationalInstitutesofHealth.There,sheledalabthatstudiedmetabolicriskfactorsforcardiovasculardiseaseaspartofthe,apioneeringlong-termpopulationstudyofcardiovasculardisease.But,shenotes,theshifttoMSDwasarelativelyeasyone.IwasimpressedbyMSDseffortstoleveragehumangeneticstodrivedrugdiscovery,shesays.Forme,itwastheperfectnextstepfromtheworkthatIhadbeendoinginacademia.Genetics:TheNewFrontierWe'relucky—CarolinespassionforgeneticsisagreatfitforMSD.Inourlabsandacrosstheindustry,weareseeinganincreaseduseofhumangeneticstohelpdeterminewhetherpatientswillrespondtoacertaindrugornot,ShepointstoMSD'sactiveresearchcollaborationswithscientistsaroundtheworldaimedatadvancingthisfieldofscience.Iamveryenthusiasticaboutwhereourresearchmaylead.CarolineFox,M.D.ispassionateaboutgenetics.Inmedicalschool,shestudiedtheeffectsoftheenvironmentondiabetesandobesityonatribeofNativeAmericans(certainpopulationsworldwidehaveagreaterpropensitytowardsdiabetes;thistribewasonesuchgroup).Herresearchlefthermotivatedtolearnmoreabouthowgeneticsplaysaroleinmetabolicdiseases.Thatwasmystart,shenotes.Sincethen,almostallofmyresearchhasbeenfocusedonuncoveringthegeneticfoundationsofthesetypesofdiseases.ChangingPerceptionsPriortojoiningMSDResearchLaboratoriesinBoston,CarolineworkedattheNationalInstitutesofHealth.There,sheledalabthatstudiedmetabolicriskfactorsforcardiovasculardiseaseaspartofthe,apioneeringlong-termpopulationstudyofcardiovasculardisease.But,shenotes,theshifttoMSDwasarelativelyeasyone.IwasimpressedbyMSDseffortstoleveragehumangeneticstodrivedrugdiscovery,shesays.Forme,itwastheperfectnextstepfromtheworkthatIhadbeendoinginacademia.Genetics:TheNewFrontierWe'relucky—CarolinespassionforgeneticsisagreatfitforMSD.Inourlabsandacrosstheindustry,weareseeinganincreaseduseofhumangeneticstohelpdeterminewhetherpatientswillrespondtoacertaindrugornot,ShepointstoMSD'sactiveresearchcollaborationswithscientistsaroundtheworldaimedatadvancingthisfieldofscience.Iamveryenthusiasticaboutwhereourresearchmaylead.Historically,oncologypracticeandclinicaltrialdesignprimarilyfocusedonwherethetumorfirstemerged,suchascolonorrectum,lung,breast,andendometrium.Thisapproachfollowsthelogicofthescalpel:pinpointingthelocationofthetumorfirstenabledsurgicalplans.Morerecently,therehavebeensignificantadvancesinourunderstandingoftheroleofcancerbiomarkersinmolecularandcellularmechanismsthatcandrivetumorgrowth.Biomarkersarebiologicalmolecules(typicallycomprisedofDNA,RNAorprotein)foundintissuesorbloodthatcanserveasasigntobetterunderstandaconditionordisease.Sometimes,thesamebiomarkerisfoundacrossmanydifferenttypesofcancer,regardlessofwherethetumorfirstdeveloped.Withinaspecifictumorlocation,thesebiomarkerscansometimesdifferentiatewhetherthetumorislikelytorespondtoagiventreatment.Assuch,thesebiomarkershavebeenusedtohelpinformclinicalresearch,acceleratingtheprocessofgettingtargetedmedicinestopatientswhereseparatetrialswouldtakeyearstoconduct.Importantly,insomecases,thesefeaturescanbeassessedusinglaboratoryteststhathavelongbeenavailable.Whereatestiseithernotavailable,orforresearchuseonly,thetestmanufacturerpartnerswiththedrugmanufacturertoadvancetogetherintoregulatoryapprovalbygovernmentagencies(suchastheFDA)acompaniondiagnosticassaytoensuresafeandeffectiveuseofthedruginpatientslikelytorespond.Thegoalistouseadeeperunderstandingofthetumorbiologyandassociatedbiomarkerstotackletumorresearchmoreprecisely;goingbeyondsimplywhereatumorarose.Instead,wearelearninghowtoattackacancerbasedonitsbiologyatthecellularlevel.AtMSD,effortsareunderwaytobetterunderstandmicrosatelliteinstability(MSI)andmismatchrepairdeficiency(dMMR).Thesebiomarkersarepresentacrosstumortypes,regardlessoftheoriginallocationofthecancer.ThepresenceofhighlevelsofMSI(MSI-H)ordMMRsignifiesanunderlyingprobleminacell'sabilitytofixerrorsthatoccurwhenDNAreplicates.TumorcellsdeterminedtohaveMSI-HordMMRharborhundredstothousandsofmutations.Theultimateproofofoureffortswillmanifestasanewgenerationofcancermedicines:thosethatfollowthelogicofbiology,notthelogicofthescalpel.

  Historically,oncologypracticeandclinicaltrialdesignprimarilyfocusedonwherethetumorfirstemerged,suchascolonorrectum,lung,breast,andendometrium.Thisapproachfollowsthelogicofthescalpel:pinpointingthelocationofthetumorfirstenabledsurgicalplans.Morerecently,therehavebeensignificantadvancesinourunderstandingoftheroleofcancerbiomarkersinmolecularandcellularmechanismsthatcandrivetumorgrowth.Biomarkersarebiologicalmolecules(typicallycomprisedofDNA,RNAorprotein)foundintissuesorbloodthatcanserveasasigntobetterunderstandaconditionordisease.Sometimes,thesamebiomarkerisfoundacrossmanydifferenttypesofcancer,regardlessofwherethetumorfirstdeveloped.Withinaspecifictumorlocation,thesebiomarkerscansometimesdifferentiatewhetherthetumorislikelytorespondtoagiventreatment.Assuch,thesebiomarkershavebeenusedtohelpinformclinicalresearch,acceleratingtheprocessofgettingtargetedmedicinestopatientswhereseparatetrialswouldtakeyearstoconduct.Importantly,insomecases,thesefeaturescanbeassessedusinglaboratoryteststhathavelongbeenavailable.Whereatestiseithernotavailable,orforresearchuseonly,thetestmanufacturerpartnerswiththedrugmanufacturertoadvancetogetherintoregulatoryapprovalbygovernmentagencies(suchastheFDA)acompaniondiagnosticassaytoensuresafeandeffectiveuseofthedruginpatientslikelytorespond.Thegoalistouseadeeperunderstandingofthetumorbiologyandassociatedbiomarkerstotackletumorresearchmoreprecisely;goingbeyondsimplywhereatumorarose.Instead,wearelearninghowtoattackacancerbasedonitsbiologyatthecellularlevel.AtMSD,effortsareunderwaytobetterunderstandmicrosatelliteinstability(MSI)andmismatchrepairdeficiency(dMMR).Thesebiomarkersarepresentacrosstumortypes,regardlessoftheoriginallocationofthecancer.ThepresenceofhighlevelsofMSI(MSI-H)ordMMRsignifiesanunderlyingprobleminacell'sabilitytofixerrorsthatoccurwhenDNAreplicates.TumorcellsdeterminedtohaveMSI-HordMMRharborhundredstothousandsofmutations.Theultimateproofofoureffortswillmanifestasanewgenerationofcancermedicines:thosethatfollowthelogicofbiology,notthelogicofthescalpel.Ourcompanyiscommittedtodiscoveringsmart,sustainablewaystoexpandaccesstohealthcare,especiallyinareaswithlimitedinfrastructureandresources.Giventhesignificanceofthischallenge,itisonlybyworkinginpartnershipwithothers—governments,donors,patientorganizations,healthcareprofessionals,NGOs,academicinstitutions,multilateralorganizationsandtheprivatesector—thatwecanwemakethestrongestcontribution.TheMSDFellowshipforGlobalHealthisbuiltonthenotionofpartneringtostrengthenthecapacityandreachofnonprofitorganizationswhich,inturn,willultimatelysolvesomeoftheworld’sgreatesthealthcarechallenges.Jameslikeslogicpuzzles.Andwordproblems.Luckily,hegetstoapplytheseinterestsinhisworkeveryday.Jamesisacomputationalchemist–heworkswithMSD’schemistryteams,applyingpredictivemodellingtoidentifywaystodesigndrugsandanalyzedatatohelpourscientistsprioritizethenextcompoundstomakeandtest.Althoughthesearecomplexproblemsandcomplexquestionsthatwe’retryingtosolve,wetakelogicalsteps,explainsJames.Foreveryquestion,there’sreallyananswer,yousometimesjusthavetospendalittlebitmoretimethinkingaboutit,andtakeastepbackandlookatwhat’sactuallyinfrontofyou.Bettermolecules,fasterInourgroup’sroleindrugdiscovery,wehavethismantraof‘bettermolecules,faster,saysJames.Ifachemisthas100compoundsthatshe’sthinkingaboutmaking,computationally,wecanhelpprioritizewhichonestostartwithbasedonrationaldrugdesign.Jamesenjoysbeingpartofateamworkingtoachieveasingulargoal:tocreatemedicinesthatwillhelpthepeoplewhoneedthem.And,hebelievesthatcollaborationisveryimportantforresearchanddevelopment:Youcan'tdoaprojectonyourown;youneedotherstoassistandhelp,notjustbycontributingintheirindividualrole,butalsowiththeirthinking.Jamesandhiscolleagueshavealotofexperiencewithperseveranceanddetermination,too.Ourteamsofscientistsdesign,developandscreenthousandsofcompoundsandantibodiestoultimatelyadvanceonlyafewofthemostpromisingleadcandidatesintoclinicaltesting.Moleculardesignanddevelopmentisaniterativeprocess.Youhavetostickwithit.It'scontinuouslymakingmodificationsandadaptingandevolving,eventuallygettingdowntheroadorthepipelinetomakeadrug…that'swhat'sexcitingaboutit.It’sallaboutthepatientsEveryday,IcometoworkknowingthatI’mworkingtomakeadrug.And,Idon'tknowiftodayI’mgoingtoopenupanemailwithresultssaying,‘we'veaccomplishedthisor‘weneedtochangethat.’Butregardlessofwhatthoseresultsare,it'sgoingtobeprogresstogettothatendpoint.”

  Historically,oncologypracticeandclinicaltrialdesignprimarilyfocusedonwherethetumorfirstemerged,suchascolonorrectum,lung,breast,andendometrium.Thisapproachfollowsthelogicofthescalpel:pinpointingthelocationofthetumorfirstenabledsurgicalplans.Morerecently,therehavebeensignificantadvancesinourunderstandingoftheroleofcancerbiomarkersinmolecularandcellularmechanismsthatcandrivetumorgrowth.Biomarkersarebiologicalmolecules(typicallycomprisedofDNA,RNAorprotein)foundintissuesorbloodthatcanserveasasigntobetterunderstandaconditionordisease.Sometimes,thesamebiomarkerisfoundacrossmanydifferenttypesofcancer,regardlessofwherethetumorfirstdeveloped.Withinaspecifictumorlocation,thesebiomarkerscansometimesdifferentiatewhetherthetumorislikelytorespondtoagiventreatment.Assuch,thesebiomarkershavebeenusedtohelpinformclinicalresearch,acceleratingtheprocessofgettingtargetedmedicinestopatientswhereseparatetrialswouldtakeyearstoconduct.Importantly,insomecases,thesefeaturescanbeassessedusinglaboratoryteststhathavelongbeenavailable.Whereatestiseithernotavailable,orforresearchuseonly,thetestmanufacturerpartnerswiththedrugmanufacturertoadvancetogetherintoregulatoryapprovalbygovernmentagencies(suchastheFDA)acompaniondiagnosticassaytoensuresafeandeffectiveuseofthedruginpatientslikelytorespond.Thegoalistouseadeeperunderstandingofthetumorbiologyandassociatedbiomarkerstotackletumorresearchmoreprecisely;goingbeyondsimplywhereatumorarose.Instead,wearelearninghowtoattackacancerbasedonitsbiologyatthecellularlevel.AtMSD,effortsareunderwaytobetterunderstandmicrosatelliteinstability(MSI)andmismatchrepairdeficiency(dMMR).Thesebiomarkersarepresentacrosstumortypes,regardlessoftheoriginallocationofthecancer.ThepresenceofhighlevelsofMSI(MSI-H)ordMMRsignifiesanunderlyingprobleminacell'sabilitytofixerrorsthatoccurwhenDNAreplicates.TumorcellsdeterminedtohaveMSI-HordMMRharborhundredstothousandsofmutations.Theultimateproofofoureffortswillmanifestasanewgenerationofcancermedicines:thosethatfollowthelogicofbiology,notthelogicofthescalpel.Chemistryhasbeencentraltoourbusinessofsinceourearliestdaysasacompany.Historically,ourdrugdiscoveryprocessprimarilycenteredaroundsmallmolecules.Then,thebirthofbiotechnologyinthelate1970s/early1980saddedbiologics,orengineeredproteins,tothemix.Today,newmodalitiesareemergingthatshowastrongpotentialtotargetcomplexdiseasesthathavenotyetbeenreachablewitheithersmallmoleculesorbiologics.RobGarbaccioisleadingatalentedteamofchemistswhoarehelpingguideMSD’sentryintothisexcitingnewfieldofmedicine.IntroducinganddiscoveringnewwaysforwardRobistheassociatevicepresident,ChemistryCapabilitiesforAcceleratingTherapeutics(CCAT),adiscoverychemistryteamthatislookingathowtogobeyondthetraditionalmethodsofdiscoveringanddevelopingmedicines."Therearecertaindiseasetargetsthatarereallyhardto'reach'andimpactusingtraditionalmethods,"henotes."SopartofthegroupIoverseetriestofigureouthowwecanemploynewermodalities,suchaspeptides,bioconjugates,andoligonucleotides,toaddressthechallengingtargetsthatareincreasinglyemergingfrombiologicalresearch."Rob'sgroupisnotfocusedonanyspecifictherapeuticarea--theyareseekingnewwaystoaddressthemostdifficultdiseasetargets."Inoncology,infectiousdiseases,andneuroscience,forexample,we’relookingforthosetargetsthatourcolleaguessay,'Ifonlywecouldmodulatethistarget,webelievewemightbeabletopotentiallyinterruptthediseaseprocessandhelppatients,'"henotes.Using‘creativechemistry’totreatdiseaseIt'scomplexwork,tobesure,butthat'swhatmakesitsointriguingandinspiringforRobandhisteam."ThethingthatIlikethemostaboutmyworkisthebeliefthattheremaybeapathforwardforthetreatmentofeachandeveryoneofthesediseases.Wejustcan'tseeityetbecausethebiologyissocomplex,"saysRob."Asresearcherscontinuetoimproveourunderstandingofdiseasebiology,Ibelievethatcombiningthatknowledgewithcreativechemistrywillhelpleadusdownnewroadstotreatingdiseaseandhelpingpatients."Robjoinedthecompanyaftercompletinggraduateschoolandapostdoctoralfellowshipfocusingonorganicchemistry."Icameherebecausescienceandinnovationdrivethiscompany.I'mpassionateaboutourmissiontosaveandimprovelives,andIbelievethatmybestdayatwork,thedaymyteammakesapotentiallylife-changingdiscovery,isstillaheadofme,andit'sthereasonthatIstay."InventingforlifeAtMSD,wesayweare.AndRobdefinitelyseeshimselfasaninventor."Chemistshavethisuniqueabilitytocombineatomsandbondsbetweenatomsinauniqueway.Everydaychemistsareinventinghundredsofmoleculesthathaveneverexistedbefore.So,yes,weareinventing,"hesays."Weareinventingtosolveproblems."Chemistryhasbeencentraltoourbusinessofsinceourearliestdaysasacompany.Historically,ourdrugdiscoveryprocessprimarilycenteredaroundsmallmolecules.Then,thebirthofbiotechnologyinthelate1970s/early1980saddedbiologics,orengineeredproteins,tothemix.Today,newmodalitiesareemergingthatshowastrongpotentialtotargetcomplexdiseasesthathavenotyetbeenreachablewitheithersmallmoleculesorbiologics.RobGarbaccioisleadingatalentedteamofchemistswhoarehelpingguideMSD’sentryintothisexcitingnewfieldofmedicine.IntroducinganddiscoveringnewwaysforwardRobistheassociatevicepresident,ChemistryCapabilitiesforAcceleratingTherapeutics(CCAT),adiscoverychemistryteamthatislookingathowtogobeyondthetraditionalmethodsofdiscoveringanddevelopingmedicines."Therearecertaindiseasetargetsthatarereallyhardto'reach'andimpactusingtraditionalmethods,"henotes."SopartofthegroupIoverseetriestofigureouthowwecanemploynewermodalities,suchaspeptides,bioconjugates,andoligonucleotides,toaddressthechallengingtargetsthatareincreasinglyemergingfrombiologicalresearch."Rob'sgroupisnotfocusedonanyspecifictherapeuticarea--theyareseekingnewwaystoaddressthemostdifficultdiseasetargets."Inoncology,infectiousdiseases,andneuroscience,forexample,we’relookingforthosetargetsthatourcolleaguessay,'Ifonlywecouldmodulatethistarget,webelievewemightbeabletopotentiallyinterruptthediseaseprocessandhelppatients,'"henotes.Using‘creativechemistry’totreatdiseaseIt'scomplexwork,tobesure,butthat'swhatmakesitsointriguingandinspiringforRobandhisteam."ThethingthatIlikethemostaboutmyworkisthebeliefthattheremaybeapathforwardforthetreatmentofeachandeveryoneofthesediseases.Wejustcan'tseeityetbecausethebiologyissocomplex,"saysRob."Asresearcherscontinuetoimproveourunderstandingofdiseasebiology,Ibelievethatcombiningthatknowledgewithcreativechemistrywillhelpleadusdownnewroadstotreatingdiseaseandhelpingpatients."Robjoinedthecompanyaftercompletinggraduateschoolandapostdoctoralfellowshipfocusingonorganicchemistry."Icameherebecausescienceandinnovationdrivethiscompany.I'mpassionateaboutourmissiontosaveandimprovelives,andIbelievethatmybestdayatwork,thedaymyteammakesapotentiallylife-changingdiscovery,isstillaheadofme,andit'sthereasonthatIstay."InventingforlifeAtMSD,wesayweare.AndRobdefinitelyseeshimselfasaninventor."Chemistshavethisuniqueabilitytocombineatomsandbondsbetweenatomsinauniqueway.Everydaychemistsareinventinghundredsofmoleculesthathaveneverexistedbefore.So,yes,weareinventing,"hesays."Weareinventingtosolveproblems."

  Chemistryhasbeencentraltoourbusinessofsinceourearliestdaysasacompany.Historically,ourdrugdiscoveryprocessprimarilycenteredaroundsmallmolecules.Then,thebirthofbiotechnologyinthelate1970s/early1980saddedbiologics,orengineeredproteins,tothemix.Today,newmodalitiesareemergingthatshowastrongpotentialtotargetcomplexdiseasesthathavenotyetbeenreachablewitheithersmallmoleculesorbiologics.RobGarbaccioisleadingatalentedteamofchemistswhoarehelpingguideMSD’sentryintothisexcitingnewfieldofmedicine.IntroducinganddiscoveringnewwaysforwardRobistheassociatevicepresident,ChemistryCapabilitiesforAcceleratingTherapeutics(CCAT),adiscoverychemistryteamthatislookingathowtogobeyondthetraditionalmethodsofdiscoveringanddevelopingmedicines."Therearecertaindiseasetargetsthatarereallyhardto'reach'andimpactusingtraditionalmethods,"henotes."SopartofthegroupIoverseetriestofigureouthowwecanemploynewermodalities,suchaspeptides,bioconjugates,andoligonucleotides,toaddressthechallengingtargetsthatareincreasinglyemergingfrombiologicalresearch."Rob'sgroupisnotfocusedonanyspecifictherapeuticarea--theyareseekingnewwaystoaddressthemostdifficultdiseasetargets."Inoncology,infectiousdiseases,andneuroscience,forexample,we’relookingforthosetargetsthatourcolleaguessay,'Ifonlywecouldmodulatethistarget,webelievewemightbeabletopotentiallyinterruptthediseaseprocessandhelppatients,'"henotes.Using‘creativechemistry’totreatdiseaseIt'scomplexwork,tobesure,butthat'swhatmakesitsointriguingandinspiringforRobandhisteam."ThethingthatIlikethemostaboutmyworkisthebeliefthattheremaybeapathforwardforthetreatmentofeachandeveryoneofthesediseases.Wejustcan'tseeityetbecausethebiologyissocomplex,"saysRob."Asresearcherscontinuetoimproveourunderstandingofdiseasebiology,Ibelievethatcombiningthatknowledgewithcreativechemistrywillhelpleadusdownnewroadstotreatingdiseaseandhelpingpatients."Robjoinedthecompanyaftercompletinggraduateschoolandapostdoctoralfellowshipfocusingonorganicchemistry."Icameherebecausescienceandinnovationdrivethiscompany.I'mpassionateaboutourmissiontosaveandimprovelives,andIbelievethatmybestdayatwork,thedaymyteammakesapotentiallylife-changingdiscovery,isstillaheadofme,andit'sthereasonthatIstay."InventingforlifeAtMSD,wesayweare.AndRobdefinitelyseeshimselfasaninventor."Chemistshavethisuniqueabilitytocombineatomsandbondsbetweenatomsinauniqueway.Everydaychemistsareinventinghundredsofmoleculesthathaveneverexistedbefore.So,yes,weareinventing,"hesays."Weareinventingtosolveproblems."Historically,oncologypracticeandclinicaltrialdesignprimarilyfocusedonwherethetumorfirstemerged,suchascolonorrectum,lung,breast,andendometrium.Thisapproachfollowsthelogicofthescalpel:pinpointingthelocationofthetumorfirstenabledsurgicalplans.Morerecently,therehavebeensignificantadvancesinourunderstandingoftheroleofcancerbiomarkersinmolecularandcellularmechanismsthatcandrivetumorgrowth.Biomarkersarebiologicalmolecules(typicallycomprisedofDNA,RNAorprotein)foundintissuesorbloodthatcanserveasasigntobetterunderstandaconditionordisease.Sometimes,thesamebiomarkerisfoundacrossmanydifferenttypesofcancer,regardlessofwherethetumorfirstdeveloped.Withinaspecifictumorlocation,thesebiomarkerscansometimesdifferentiatewhetherthetumorislikelytorespondtoagiventreatment.Assuch,thesebiomarkershavebeenusedtohelpinformclinicalresearch,acceleratingtheprocessofgettingtargetedmedicinestopatientswhereseparatetrialswouldtakeyearstoconduct.Importantly,insomecases,thesefeaturescanbeassessedusinglaboratoryteststhathavelongbeenavailable.Whereatestiseithernotavailable,orforresearchuseonly,thetestmanufacturerpartnerswiththedrugmanufacturertoadvancetogetherintoregulatoryapprovalbygovernmentagencies(suchastheFDA)acompaniondiagnosticassaytoensuresafeandeffectiveuseofthedruginpatientslikelytorespond.Thegoalistouseadeeperunderstandingofthetumorbiologyandassociatedbiomarkerstotackletumorresearchmoreprecisely;goingbeyondsimplywhereatumorarose.Instead,wearelearninghowtoattackacancerbasedonitsbiologyatthecellularlevel.AtMSD,effortsareunderwaytobetterunderstandmicrosatelliteinstability(MSI)andmismatchrepairdeficiency(dMMR).Thesebiomarkersarepresentacrosstumortypes,regardlessoftheoriginallocationofthecancer.ThepresenceofhighlevelsofMSI(MSI-H)ordMMRsignifiesanunderlyingprobleminacell'sabilitytofixerrorsthatoccurwhenDNAreplicates.TumorcellsdeterminedtohaveMSI-HordMMRharborhundredstothousandsofmutations.Theultimateproofofoureffortswillmanifestasanewgenerationofcancermedicines:thosethatfollowthelogicofbiology,notthelogicofthescalpel.“MyuncleIvanwasaseverediabetespatient—heneededinjectionsthreetimesaday.Hewaswithoutinsulinformorethanamonth.EvenIwasnotaware,”Pablorecounts.“Whenhefinallyreceivedinsulin,hewasinbadcondition.Severalweekslater,hishealthdeclined,hehadrenalfailure,andhedied.”ThedroneteamrecentlyacknowledgedPablo’scontributions,andhispersonalloss,bygivingtheprojectanewnickname.Oncecalled“MajorTom”aftertheDavidBowiesong,it’snow“ProjectIvan.”“Idon’thavewordsenoughtoshowmygratitude,”Pablosays.“Thisisaboutsavinglives.”

  Toexpressourappreciation,MSDbegan#DearCancerHeroes–asocialmediacampaigntorecognizetheirfortitudeandcontributionstothefield.It’sasmallgesturetoshowourgratitude.Wewanttoletclinicaltrialparticipantsknowtheyarenotaloneandthereisawholecommunityofpeoplecheeringthemon.Anyonecanjointhemovementbywritingamessagetocancerclinicaltrialparticipantsonastickynoteandsharingitonsocialmediausing#DearCancerHeroes.Cancerresearchhascomealongwayandstillhasalongwaytogo.However,wewouldn’thavegottentowherewearetodaywithouttheseheroes.CarolineFox,M.D.ispassionateaboutgenetics.Inmedicalschool,shestudiedtheeffectsoftheenvironmentondiabetesandobesityonatribeofNativeAmericans(certainpopulationsworldwidehaveagreaterpropensitytowardsdiabetes;thistribewasonesuchgroup).Herresearchlefthermotivatedtolearnmoreabouthowgeneticsplaysaroleinmetabolicdiseases.Thatwasmystart,shenotes.Sincethen,almostallofmyresearchhasbeenfocusedonuncoveringthegeneticfoundationsofthesetypesofdiseases.ChangingPerceptionsPriortojoiningMSDResearchLaboratoriesinBoston,CarolineworkedattheNationalInstitutesofHealth.There,sheledalabthatstudiedmetabolicriskfactorsforcardiovasculardiseaseaspartofthe,apioneeringlong-termpopulationstudyofcardiovasculardisease.But,shenotes,theshifttoMSDwasarelativelyeasyone.IwasimpressedbyMSDseffortstoleveragehumangeneticstodrivedrugdiscovery,shesays.Forme,itwastheperfectnextstepfromtheworkthatIhadbeendoinginacademia.Genetics:TheNewFrontierWe'relucky—CarolinespassionforgeneticsisagreatfitforMSD.Inourlabsandacrosstheindustry,weareseeinganincreaseduseofhumangeneticstohelpdeterminewhetherpatientswillrespondtoacertaindrugornot,ShepointstoMSD'sactiveresearchcollaborationswithscientistsaroundtheworldaimedatadvancingthisfieldofscience.Iamveryenthusiasticaboutwhereourresearchmaylead.“MyuncleIvanwasaseverediabetespatient—heneededinjectionsthreetimesaday.Hewaswithoutinsulinformorethanamonth.EvenIwasnotaware,”Pablorecounts.“Whenhefinallyreceivedinsulin,hewasinbadcondition.Severalweekslater,hishealthdeclined,hehadrenalfailure,andhedied.”ThedroneteamrecentlyacknowledgedPablo’scontributions,andhispersonalloss,bygivingtheprojectanewnickname.Oncecalled“MajorTom”aftertheDavidBowiesong,it’snow“ProjectIvan.”“Idon’thavewordsenoughtoshowmygratitude,”Pablosays.“Thisisaboutsavinglives.”

  Jameslikeslogicpuzzles.Andwordproblems.Luckily,hegetstoapplytheseinterestsinhisworkeveryday.Jamesisacomputationalchemist–heworkswithMSD’schemistryteams,applyingpredictivemodellingtoidentifywaystodesigndrugsandanalyzedatatohelpourscientistsprioritizethenextcompoundstomakeandtest.Althoughthesearecomplexproblemsandcomplexquestionsthatwe’retryingtosolve,wetakelogicalsteps,explainsJames.Foreveryquestion,there’sreallyananswer,yousometimesjusthavetospendalittlebitmoretimethinkingaboutit,andtakeastepbackandlookatwhat’sactuallyinfrontofyou.Bettermolecules,fasterInourgroup’sroleindrugdiscovery,wehavethismantraof‘bettermolecules,faster,saysJames.Ifachemisthas100compoundsthatshe’sthinkingaboutmaking,computationally,wecanhelpprioritizewhichonestostartwithbasedonrationaldrugdesign.Jamesenjoysbeingpartofateamworkingtoachieveasingulargoal:tocreatemedicinesthatwillhelpthepeoplewhoneedthem.And,hebelievesthatcollaborationisveryimportantforresearchanddevelopment:Youcan'tdoaprojectonyourown;youneedotherstoassistandhelp,notjustbycontributingintheirindividualrole,butalsowiththeirthinking.Jamesandhiscolleagueshavealotofexperiencewithperseveranceanddetermination,too.Ourteamsofscientistsdesign,developandscreenthousandsofcompoundsandantibodiestoultimatelyadvanceonlyafewofthemostpromisingleadcandidatesintoclinicaltesting.Moleculardesignanddevelopmentisaniterativeprocess.Youhavetostickwithit.It'scontinuouslymakingmodificationsandadaptingandevolving,eventuallygettingdowntheroadorthepipelinetomakeadrug…that'swhat'sexcitingaboutit.It’sallaboutthepatientsEveryday,IcometoworkknowingthatI’mworkingtomakeadrug.And,Idon'tknowiftodayI’mgoingtoopenupanemailwithresultssaying,‘we'veaccomplishedthisor‘weneedtochangethat.’Butregardlessofwhatthoseresultsare,it'sgoingtobeprogresstogettothatendpoint.”Chemistryhasbeencentraltoourbusinessofsinceourearliestdaysasacompany.Historically,ourdrugdiscoveryprocessprimarilycenteredaroundsmallmolecules.Then,thebirthofbiotechnologyinthelate1970s/early1980saddedbiologics,orengineeredproteins,tothemix.Today,newmodalitiesareemergingthatshowastrongpotentialtotargetcomplexdiseasesthathavenotyetbeenreachablewitheithersmallmoleculesorbiologics.RobGarbaccioisleadingatalentedteamofchemistswhoarehelpingguideMSD’sentryintothisexcitingnewfieldofmedicine.IntroducinganddiscoveringnewwaysforwardRobistheassociatevicepresident,ChemistryCapabilitiesforAcceleratingTherapeutics(CCAT),adiscoverychemistryteamthatislookingathowtogobeyondthetraditionalmethodsofdiscoveringanddevelopingmedicines."Therearecertaindiseasetargetsthatarereallyhardto'reach'andimpactusingtraditionalmethods,"henotes."SopartofthegroupIoverseetriestofigureouthowwecanemploynewermodalities,suchaspeptides,bioconjugates,andoligonucleotides,toaddressthechallengingtargetsthatareincreasinglyemergingfrombiologicalresearch."Rob'sgroupisnotfocusedonanyspecifictherapeuticarea--theyareseekingnewwaystoaddressthemostdifficultdiseasetargets."Inoncology,infectiousdiseases,andneuroscience,forexample,we’relookingforthosetargetsthatourcolleaguessay,'Ifonlywecouldmodulatethistarget,webelievewemightbeabletopotentiallyinterruptthediseaseprocessandhelppatients,'"henotes.Using‘creativechemistry’totreatdiseaseIt'scomplexwork,tobesure,butthat'swhatmakesitsointriguingandinspiringforRobandhisteam."ThethingthatIlikethemostaboutmyworkisthebeliefthattheremaybeapathforwardforthetreatmentofeachandeveryoneofthesediseases.Wejustcan'tseeityetbecausethebiologyissocomplex,"saysRob."Asresearcherscontinuetoimproveourunderstandingofdiseasebiology,Ibelievethatcombiningthatknowledgewithcreativechemistrywillhelpleadusdownnewroadstotreatingdiseaseandhelpingpatients."Robjoinedthecompanyaftercompletinggraduateschoolandapostdoctoralfellowshipfocusingonorganicchemistry."Icameherebecausescienceandinnovationdrivethiscompany.I'mpassionateaboutourmissiontosaveandimprovelives,andIbelievethatmybestdayatwork,thedaymyteammakesapotentiallylife-changingdiscovery,isstillaheadofme,andit'sthereasonthatIstay."InventingforlifeAtMSD,wesayweare.AndRobdefinitelyseeshimselfasaninventor."Chemistshavethisuniqueabilitytocombineatomsandbondsbetweenatomsinauniqueway.Everydaychemistsareinventinghundredsofmoleculesthathaveneverexistedbefore.So,yes,weareinventing,"hesays."Weareinventingtosolveproblems."In1962hercollaborators,JamesWatson,FrancisCrickandMauriceWilkinswereawardedtheNobelPrizefortheir“discoveriesconcerningthemolecularstructureofnucleicacidsanditssignificanceforinformationtransferinlivingmaterial.”Franklin’suntimelydeathdeniedhertheacclaimofthisprestigiousscientificaward(theNobelCommitteedoesnotawardtheprizeposthumously),butherroleinthisfundamentaldiscoveryhasbeenwelldocumentedandisnowwidelyrecognized.Franklin’sstoryofalifecutshortbyovariancancerremainsalltoocommon.Eventoday,advancedovariancancerremainsoneofthemostdifficultcancerstotreat.Butthereremainsareasonforoptimism.Thepaceofchangeincancertreatmenthasincreaseddramaticallyinrecentyears.Advancesinresearch–manyofwhichmaybetracedbacktoFranklin’swork–havegivenusadeeperunderstandingofhowtotargetthedisease,pavingthewayfornewdevelopments.Specifictoovariancancer,recentclinicalresearchhasshownpromiseforwomenwithadvancedstagesofthedisease.AtMSD,wearefocusedontranslatingbreakthroughscienceintooncologytherapeuticsthathavethegreatestpotentialforimprovinglong-termdiseasecontrolandsurvivalforpatients,includingthosewithovariancancer.Werecognizethatnotwopatientsorcancersarethesameandmultipleapproaches–therapeuticregimensandmechanismsofaction–willbeneededtooutpacethisdisease.That’swhywehaveworkedrigorouslytoexpandanddiversifyourowninternalresearchprograms.Thereisstillworktobedone,butwebelievestronglyinourpotentialtotransformthewayallcancersaretreated.AndweareconstantlyinspiredtoworkharderbystorieslikeRosalindFranklin’s.

  Ourcompanyiscommittedtodiscoveringsmart,sustainablewaystoexpandaccesstohealthcare,especiallyinareaswithlimitedinfrastructureandresources.Giventhesignificanceofthischallenge,itisonlybyworkinginpartnershipwithothers—governments,donors,patientorganizations,healthcareprofessionals,NGOs,academicinstitutions,multilateralorganizationsandtheprivatesector—thatwecanwemakethestrongestcontribution.TheMSDFellowshipforGlobalHealthisbuiltonthenotionofpartneringtostrengthenthecapacityandreachofnonprofitorganizationswhich,inturn,willultimatelysolvesomeoftheworld’sgreatesthealthcarechallenges.Dr.Chenghasbeentreatingheadandneckcancerpatientsformanyyears.Thisishispersonalperspective.Ihavetreatedpatientswithheadandneckcancersformanyyears,soIhaveseen,upclose,thedifficultexperienceoflivingwithheadandneckcancer.Cancerisatryingsituationforallpatientsandtheirlovedones,butheadandneckpatientsfacecancerinauniqueanddifficultway,withtheirdiseaseandtumorsoftenvisibletothepublic.Ihavebeeninvolvedinresearchforyearsaspartofscientists'decades-longendeavortobringforwardmeaningfuladvancesforpatientsdiagnosedwiththispotentiallyaggressivedisease.Untilrecently,suchadvanceswerehardtocomebyandmypatientsandIstruggledwiththelimitedtreatmentoptionsavailable.Butwhilethereisasignificantneedfornewtreatmentoptions,thegoodnewsisthattherehavebeensomeimprovementsinsurvivalratesovertheyearsandweareseeinganewandencouragingfutureahead.Wehavebeguntoleverageourunderstandingofbiologytodevelopmoreprecisetherapies.AtMSD,wearefocusedonimmuno-oncologyresearch,whichstudiestheroleoftheimmunesystemindetectingandfightingcancer.Wearestudyingthepotentialofthisapproach,whichaimstoharnessandrestorethebodysabilitytodetectandfightcancercells,inanumberofcancers,includingheadandneckcancer.Immuno-oncologyhasalreadysignificantlychangedthewaycertaincancersaretreated,includingmelanomaandlungcancer,aswellasinthetreatmentofheadandneckcancer.Changeiscomingtotheheadandneckcancerlandscape–anditisthrillingtobeapartofit.TobeabletoseehowourresearchandeffortsatMSDarehavingadirectimpactonhowphysiciansapproachthetreatmentoftheirpatientsandwhatpatientsmayexpectfromtheirtreatmentiswhatmotivatesustoworkharder.Dr.Chenghasbeentreatingheadandneckcancerpatientsformanyyears.Thisishispersonalperspective.Ihavetreatedpatientswithheadandneckcancersformanyyears,soIhaveseen,upclose,thedifficultexperienceoflivingwithheadandneckcancer.Cancerisatryingsituationforallpatientsandtheirlovedones,butheadandneckpatientsfacecancerinauniqueanddifficultway,withtheirdiseaseandtumorsoftenvisibletothepublic.Ihavebeeninvolvedinresearchforyearsaspartofscientists'decades-longendeavortobringforwardmeaningfuladvancesforpatientsdiagnosedwiththispotentiallyaggressivedisease.Untilrecently,suchadvanceswerehardtocomebyandmypatientsandIstruggledwiththelimitedtreatmentoptionsavailable.Butwhilethereisasignificantneedfornewtreatmentoptions,thegoodnewsisthattherehavebeensomeimprovementsinsurvivalratesovertheyearsandweareseeinganewandencouragingfutureahead.Wehavebeguntoleverageourunderstandingofbiologytodevelopmoreprecisetherapies.AtMSD,wearefocusedonimmuno-oncologyresearch,whichstudiestheroleoftheimmunesystemindetectingandfightingcancer.Wearestudyingthepotentialofthisapproach,whichaimstoharnessandrestorethebodysabilitytodetectandfightcancercells,inanumberofcancers,includingheadandneckcancer.Immuno-oncologyhasalreadysignificantlychangedthewaycertaincancersaretreated,includingmelanomaandlungcancer,aswellasinthetreatmentofheadandneckcancer.Changeiscomingtotheheadandneckcancerlandscape–anditisthrillingtobeapartofit.TobeabletoseehowourresearchandeffortsatMSDarehavingadirectimpactonhowphysiciansapproachthetreatmentoftheirpatientsandwhatpatientsmayexpectfromtheirtreatmentiswhatmotivatesustoworkharder.

  Ourcompanyiscommittedtodiscoveringsmart,sustainablewaystoexpandaccesstohealthcare,especiallyinareaswithlimitedinfrastructureandresources.Giventhesignificanceofthischallenge,itisonlybyworkinginpartnershipwithothers—governments,donors,patientorganizations,healthcareprofessionals,NGOs,academicinstitutions,multilateralorganizationsandtheprivatesector—thatwecanwemakethestrongestcontribution.TheMSDFellowshipforGlobalHealthisbuiltonthenotionofpartneringtostrengthenthecapacityandreachofnonprofitorganizationswhich,inturn,willultimatelysolvesomeoftheworld’sgreatesthealthcarechallenges.Dr.Chenghasbeentreatingheadandneckcancerpatientsformanyyears.Thisishispersonalperspective.Ihavetreatedpatientswithheadandneckcancersformanyyears,soIhaveseen,upclose,thedifficultexperienceoflivingwithheadandneckcancer.Cancerisatryingsituationforallpatientsandtheirlovedones,butheadandneckpatientsfacecancerinauniqueanddifficultway,withtheirdiseaseandtumorsoftenvisibletothepublic.Ihavebeeninvolvedinresearchforyearsaspartofscientists'decades-longendeavortobringforwardmeaningfuladvancesforpatientsdiagnosedwiththispotentiallyaggressivedisease.Untilrecently,suchadvanceswerehardtocomebyandmypatientsandIstruggledwiththelimitedtreatmentoptionsavailable.Butwhilethereisasignificantneedfornewtreatmentoptions,thegoodnewsisthattherehavebeensomeimprovementsinsurvivalratesovertheyearsandweareseeinganewandencouragingfutureahead.Wehavebeguntoleverageourunderstandingofbiologytodevelopmoreprecisetherapies.AtMSD,wearefocusedonimmuno-oncologyresearch,whichstudiestheroleoftheimmunesystemindetectingandfightingcancer.Wearestudyingthepotentialofthisapproach,whichaimstoharnessandrestorethebodysabilitytodetectandfightcancercells,inanumberofcancers,includingheadandneckcancer.Immuno-oncologyhasalreadysignificantlychangedthewaycertaincancersaretreated,includingmelanomaandlungcancer,aswellasinthetreatmentofheadandneckcancer.Changeiscomingtotheheadandneckcancerlandscape–anditisthrillingtobeapartofit.TobeabletoseehowourresearchandeffortsatMSDarehavingadirectimpactonhowphysiciansapproachthetreatmentoftheirpatientsandwhatpatientsmayexpectfromtheirtreatmentiswhatmotivatesustoworkharder.Dr.Chenghasbeentreatingheadandneckcancerpatientsformanyyears.Thisishispersonalperspective.Ihavetreatedpatientswithheadandneckcancersformanyyears,soIhaveseen,upclose,thedifficultexperienceoflivingwithheadandneckcancer.Cancerisatryingsituationforallpatientsandtheirlovedones,butheadandneckpatientsfacecancerinauniqueanddifficultway,withtheirdiseaseandtumorsoftenvisibletothepublic.Ihavebeeninvolvedinresearchforyearsaspartofscientists'decades-longendeavortobringforwardmeaningfuladvancesforpatientsdiagnosedwiththispotentiallyaggressivedisease.Untilrecently,suchadvanceswerehardtocomebyandmypatientsandIstruggledwiththelimitedtreatmentoptionsavailable.Butwhilethereisasignificantneedfornewtreatmentoptions,thegoodnewsisthattherehavebeensomeimprovementsinsurvivalratesovertheyearsandweareseeinganewandencouragingfutureahead.Wehavebeguntoleverageourunderstandingofbiologytodevelopmoreprecisetherapies.AtMSD,wearefocusedonimmuno-oncologyresearch,whichstudiestheroleoftheimmunesystemindetectingandfightingcancer.Wearestudyingthepotentialofthisapproach,whichaimstoharnessandrestorethebodysabilitytodetectandfightcancercells,inanumberofcancers,includingheadandneckcancer.Immuno-oncologyhasalreadysignificantlychangedthewaycertaincancersaretreated,includingmelanomaandlungcancer,aswellasinthetreatmentofheadandneckcancer.Changeiscomingtotheheadandneckcancerlandscape–anditisthrillingtobeapartofit.TobeabletoseehowourresearchandeffortsatMSDarehavingadirectimpactonhowphysiciansapproachthetreatmentoftheirpatientsandwhatpatientsmayexpectfromtheirtreatmentiswhatmotivatesustoworkharder.

  “MyuncleIvanwasaseverediabetespatient—heneededinjectionsthreetimesaday.Hewaswithoutinsulinformorethanamonth.EvenIwasnotaware,”Pablorecounts.“Whenhefinallyreceivedinsulin,hewasinbadcondition.Severalweekslater,hishealthdeclined,hehadrenalfailure,andhedied.”ThedroneteamrecentlyacknowledgedPablo’scontributions,andhispersonalloss,bygivingtheprojectanewnickname.Oncecalled“MajorTom”aftertheDavidBowiesong,it’snow“ProjectIvan.”“Idon’thavewordsenoughtoshowmygratitude,”Pablosays.“Thisisaboutsavinglives.”In1962hercollaborators,JamesWatson,FrancisCrickandMauriceWilkinswereawardedtheNobelPrizefortheir“discoveriesconcerningthemolecularstructureofnucleicacidsanditssignificanceforinformationtransferinlivingmaterial.”Franklin’suntimelydeathdeniedhertheacclaimofthisprestigiousscientificaward(theNobelCommitteedoesnotawardtheprizeposthumously),butherroleinthisfundamentaldiscoveryhasbeenwelldocumentedandisnowwidelyrecognized.Franklin’sstoryofalifecutshortbyovariancancerremainsalltoocommon.Eventoday,advancedovariancancerremainsoneofthemostdifficultcancerstotreat.Butthereremainsareasonforoptimism.Thepaceofchangeincancertreatmenthasincreaseddramaticallyinrecentyears.Advancesinresearch–manyofwhichmaybetracedbacktoFranklin’swork–havegivenusadeeperunderstandingofhowtotargetthedisease,pavingthewayfornewdevelopments.Specifictoovariancancer,recentclinicalresearchhasshownpromiseforwomenwithadvancedstagesofthedisease.AtMSD,wearefocusedontranslatingbreakthroughscienceintooncologytherapeuticsthathavethegreatestpotentialforimprovinglong-termdiseasecontrolandsurvivalforpatients,includingthosewithovariancancer.Werecognizethatnotwopatientsorcancersarethesameandmultipleapproaches–therapeuticregimensandmechanismsofaction–willbeneededtooutpacethisdisease.That’swhywehaveworkedrigorouslytoexpandanddiversifyourowninternalresearchprograms.Thereisstillworktobedone,butwebelievestronglyinourpotentialtotransformthewayallcancersaretreated.AndweareconstantlyinspiredtoworkharderbystorieslikeRosalindFranklin’s.In1962hercollaborators,JamesWatson,FrancisCrickandMauriceWilkinswereawardedtheNobelPrizefortheir“discoveriesconcerningthemolecularstructureofnucleicacidsanditssignificanceforinformationtransferinlivingmaterial.”Franklin’suntimelydeathdeniedhertheacclaimofthisprestigiousscientificaward(theNobelCommitteedoesnotawardtheprizeposthumously),butherroleinthisfundamentaldiscoveryhasbeenwelldocumentedandisnowwidelyrecognized.Franklin’sstoryofalifecutshortbyovariancancerremainsalltoocommon.Eventoday,advancedovariancancerremainsoneofthemostdifficultcancerstotreat.Butthereremainsareasonforoptimism.Thepaceofchangeincancertreatmenthasincreaseddramaticallyinrecentyears.Advancesinresearch–manyofwhichmaybetracedbacktoFranklin’swork–havegivenusadeeperunderstandingofhowtotargetthedisease,pavingthewayfornewdevelopments.Specifictoovariancancer,recentclinicalresearchhasshownpromiseforwomenwithadvancedstagesofthedisease.AtMSD,wearefocusedontranslatingbreakthroughscienceintooncologytherapeuticsthathavethegreatestpotentialforimprovinglong-termdiseasecontrolandsurvivalforpatients,includingthosewithovariancancer.Werecognizethatnotwopatientsorcancersarethesameandmultipleapproaches–therapeuticregimensandmechanismsofaction–willbeneededtooutpacethisdisease.That’swhywehaveworkedrigorouslytoexpandanddiversifyourowninternalresearchprograms.Thereisstillworktobedone,butwebelievestronglyinourpotentialtotransformthewayallcancersaretreated.AndweareconstantlyinspiredtoworkharderbystorieslikeRosalindFranklin’s.

  In1962hercollaborators,JamesWatson,FrancisCrickandMauriceWilkinswereawardedtheNobelPrizefortheir“discoveriesconcerningthemolecularstructureofnucleicacidsanditssignificanceforinformationtransferinlivingmaterial.”Franklin’suntimelydeathdeniedhertheacclaimofthisprestigiousscientificaward(theNobelCommitteedoesnotawardtheprizeposthumously),butherroleinthisfundamentaldiscoveryhasbeenwelldocumentedandisnowwidelyrecognized.Franklin’sstoryofalifecutshortbyovariancancerremainsalltoocommon.Eventoday,advancedovariancancerremainsoneofthemostdifficultcancerstotreat.Butthereremainsareasonforoptimism.Thepaceofchangeincancertreatmenthasincreaseddramaticallyinrecentyears.Advancesinresearch–manyofwhichmaybetracedbacktoFranklin’swork–havegivenusadeeperunderstandingofhowtotargetthedisease,pavingthewayfornewdevelopments.Specifictoovariancancer,recentclinicalresearchhasshownpromiseforwomenwithadvancedstagesofthedisease.AtMSD,wearefocusedontranslatingbreakthroughscienceintooncologytherapeuticsthathavethegreatestpotentialforimprovinglong-termdiseasecontrolandsurvivalforpatients,includingthosewithovariancancer.Werecognizethatnotwopatientsorcancersarethesameandmultipleapproaches–therapeuticregimensandmechanismsofaction–willbeneededtooutpacethisdisease.That’swhywehaveworkedrigorouslytoexpandanddiversifyourowninternalresearchprograms.Thereisstillworktobedone,butwebelievestronglyinourpotentialtotransformthewayallcancersaretreated.AndweareconstantlyinspiredtoworkharderbystorieslikeRosalindFranklin’s.Ourcompanyiscommittedtodiscoveringsmart,sustainablewaystoexpandaccesstohealthcare,especiallyinareaswithlimitedinfrastructureandresources.Giventhesignificanceofthischallenge,itisonlybyworkinginpartnershipwithothers—governments,donors,patientorganizations,healthcareprofessionals,NGOs,academicinstitutions,multilateralorganizationsandtheprivatesector—thatwecanwemakethestrongestcontribution.TheMSDFellowshipforGlobalHealthisbuiltonthenotionofpartneringtostrengthenthecapacityandreachofnonprofitorganizationswhich,inturn,willultimatelysolvesomeoftheworld’sgreatesthealthcarechallenges.Ourcompanyiscommittedtodiscoveringsmart,sustainablewaystoexpandaccesstohealthcare,especiallyinareaswithlimitedinfrastructureandresources.Giventhesignificanceofthischallenge,itisonlybyworkinginpartnershipwithothers—governments,donors,patientorganizations,healthcareprofessionals,NGOs,academicinstitutions,multilateralorganizationsandtheprivatesector—thatwecanwemakethestrongestcontribution.TheMSDFellowshipforGlobalHealthisbuiltonthenotionofpartneringtostrengthenthecapacityandreachofnonprofitorganizationswhich,inturn,willultimatelysolvesomeoftheworld’sgreatesthealthcarechallenges.

  Jameslikeslogicpuzzles.Andwordproblems.Luckily,hegetstoapplytheseinterestsinhisworkeveryday.Jamesisacomputationalchemist–heworkswithMSD’schemistryteams,applyingpredictivemodellingtoidentifywaystodesigndrugsandanalyzedatatohelpourscientistsprioritizethenextcompoundstomakeandtest.Althoughthesearecomplexproblemsandcomplexquestionsthatwe’retryingtosolve,wetakelogicalsteps,explainsJames.Foreveryquestion,there’sreallyananswer,yousometimesjusthavetospendalittlebitmoretimethinkingaboutit,andtakeastepbackandlookatwhat’sactuallyinfrontofyou.Bettermolecules,fasterInourgroup’sroleindrugdiscovery,wehavethismantraof‘bettermolecules,faster,saysJames.Ifachemisthas100compoundsthatshe’sthinkingaboutmaking,computationally,wecanhelpprioritizewhichonestostartwithbasedonrationaldrugdesign.Jamesenjoysbeingpartofateamworkingtoachieveasingulargoal:tocreatemedicinesthatwillhelpthepeoplewhoneedthem.And,hebelievesthatcollaborationisveryimportantforresearchanddevelopment:Youcan'tdoaprojectonyourown;youneedotherstoassistandhelp,notjustbycontributingintheirindividualrole,butalsowiththeirthinking.Jamesandhiscolleagueshavealotofexperiencewithperseveranceanddetermination,too.Ourteamsofscientistsdesign,developandscreenthousandsofcompoundsandantibodiestoultimatelyadvanceonlyafewofthemostpromisingleadcandidatesintoclinicaltesting.Moleculardesignanddevelopmentisaniterativeprocess.Youhavetostickwithit.It'scontinuouslymakingmodificationsandadaptingandevolving,eventuallygettingdowntheroadorthepipelinetomakeadrug…that'swhat'sexcitingaboutit.It’sallaboutthepatientsEveryday,IcometoworkknowingthatI’mworkingtomakeadrug.And,Idon'tknowiftodayI’mgoingtoopenupanemailwithresultssaying,‘we'veaccomplishedthisor‘weneedtochangethat.’Butregardlessofwhatthoseresultsare,it'sgoingtobeprogresstogettothatendpoint.”Historically,oncologypracticeandclinicaltrialdesignprimarilyfocusedonwherethetumorfirstemerged,suchascolonorrectum,lung,breast,andendometrium.Thisapproachfollowsthelogicofthescalpel:pinpointingthelocationofthetumorfirstenabledsurgicalplans.Morerecently,therehavebeensignificantadvancesinourunderstandingoftheroleofcancerbiomarkersinmolecularandcellularmechanismsthatcandrivetumorgrowth.Biomarkersarebiologicalmolecules(typicallycomprisedofDNA,RNAorprotein)foundintissuesorbloodthatcanserveasasigntobetterunderstandaconditionordisease.Sometimes,thesamebiomarkerisfoundacrossmanydifferenttypesofcancer,regardlessofwherethetumorfirstdeveloped.Withinaspecifictumorlocation,thesebiomarkerscansometimesdifferentiatewhetherthetumorislikelytorespondtoagiventreatment.Assuch,thesebiomarkershavebeenusedtohelpinformclinicalresearch,acceleratingtheprocessofgettingtargetedmedicinestopatientswhereseparatetrialswouldtakeyearstoconduct.Importantly,insomecases,thesefeaturescanbeassessedusinglaboratoryteststhathavelongbeenavailable.Whereatestiseithernotavailable,orforresearchuseonly,thetestmanufacturerpartnerswiththedrugmanufacturertoadvancetogetherintoregulatoryapprovalbygovernmentagencies(suchastheFDA)acompaniondiagnosticassaytoensuresafeandeffectiveuseofthedruginpatientslikelytorespond.Thegoalistouseadeeperunderstandingofthetumorbiologyandassociatedbiomarkerstotackletumorresearchmoreprecisely;goingbeyondsimplywhereatumorarose.Instead,wearelearninghowtoattackacancerbasedonitsbiologyatthecellularlevel.AtMSD,effortsareunderwaytobetterunderstandmicrosatelliteinstability(MSI)andmismatchrepairdeficiency(dMMR).Thesebiomarkersarepresentacrosstumortypes,regardlessoftheoriginallocationofthecancer.ThepresenceofhighlevelsofMSI(MSI-H)ordMMRsignifiesanunderlyingprobleminacell'sabilitytofixerrorsthatoccurwhenDNAreplicates.TumorcellsdeterminedtohaveMSI-HordMMRharborhundredstothousandsofmutations.Theultimateproofofoureffortswillmanifestasanewgenerationofcancermedicines:thosethatfollowthelogicofbiology,notthelogicofthescalpel.Chemistryhasbeencentraltoourbusinessofsinceourearliestdaysasacompany.Historically,ourdrugdiscoveryprocessprimarilycenteredaroundsmallmolecules.Then,thebirthofbiotechnologyinthelate1970s/early1980saddedbiologics,orengineeredproteins,tothemix.Today,newmodalitiesareemergingthatshowastrongpotentialtotargetcomplexdiseasesthathavenotyetbeenreachablewitheithersmallmoleculesorbiologics.RobGarbaccioisleadingatalentedteamofchemistswhoarehelpingguideMSD’sentryintothisexcitingnewfieldofmedicine.IntroducinganddiscoveringnewwaysforwardRobistheassociatevicepresident,ChemistryCapabilitiesforAcceleratingTherapeutics(CCAT),adiscoverychemistryteamthatislookingathowtogobeyondthetraditionalmethodsofdiscoveringanddevelopingmedicines."Therearecertaindiseasetargetsthatarereallyhardto'reach'andimpactusingtraditionalmethods,"henotes."SopartofthegroupIoverseetriestofigureouthowwecanemploynewermodalities,suchaspeptides,bioconjugates,andoligonucleotides,toaddressthechallengingtargetsthatareincreasinglyemergingfrombiologicalresearch."Rob'sgroupisnotfocusedonanyspecifictherapeuticarea--theyareseekingnewwaystoaddressthemostdifficultdiseasetargets."Inoncology,infectiousdiseases,andneuroscience,forexample,we’relookingforthosetargetsthatourcolleaguessay,'Ifonlywecouldmodulatethistarget,webelievewemightbeabletopotentiallyinterruptthediseaseprocessandhelppatients,'"henotes.Using‘creativechemistry’totreatdiseaseIt'scomplexwork,tobesure,butthat'swhatmakesitsointriguingandinspiringforRobandhisteam."ThethingthatIlikethemostaboutmyworkisthebeliefthattheremaybeapathforwardforthetreatmentofeachandeveryoneofthesediseases.Wejustcan'tseeityetbecausethebiologyissocomplex,"saysRob."Asresearcherscontinuetoimproveourunderstandingofdiseasebiology,Ibelievethatcombiningthatknowledgewithcreativechemistrywillhelpleadusdownnewroadstotreatingdiseaseandhelpingpatients."Robjoinedthecompanyaftercompletinggraduateschoolandapostdoctoralfellowshipfocusingonorganicchemistry."Icameherebecausescienceandinnovationdrivethiscompany.I'mpassionateaboutourmissiontosaveandimprovelives,andIbelievethatmybestdayatwork,thedaymyteammakesapotentiallylife-changingdiscovery,isstillaheadofme,andit'sthereasonthatIstay."InventingforlifeAtMSD,wesayweare.AndRobdefinitelyseeshimselfasaninventor."Chemistshavethisuniqueabilitytocombineatomsandbondsbetweenatomsinauniqueway.Everydaychemistsareinventinghundredsofmoleculesthathaveneverexistedbefore.So,yes,weareinventing,"hesays."Weareinventingtosolveproblems."

  Toexpressourappreciation,MSDbegan#DearCancerHeroes–asocialmediacampaigntorecognizetheirfortitudeandcontributionstothefield.It’sasmallgesturetoshowourgratitude.Wewanttoletclinicaltrialparticipantsknowtheyarenotaloneandthereisawholecommunityofpeoplecheeringthemon.Anyonecanjointhemovementbywritingamessagetocancerclinicaltrialparticipantsonastickynoteandsharingitonsocialmediausing#DearCancerHeroes.Cancerresearchhascomealongwayandstillhasalongwaytogo.However,wewouldn’thavegottentowherewearetodaywithouttheseheroes.“MyuncleIvanwasaseverediabetespatient—heneededinjectionsthreetimesaday.Hewaswithoutinsulinformorethanamonth.EvenIwasnotaware,”Pablorecounts.“Whenhefinallyreceivedinsulin,hewasinbadcondition.Severalweekslater,hishealthdeclined,hehadrenalfailure,andhedied.”ThedroneteamrecentlyacknowledgedPablo’scontributions,andhispersonalloss,bygivingtheprojectanewnickname.Oncecalled“MajorTom”aftertheDavidBowiesong,it’snow“ProjectIvan.”“Idon’thavewordsenoughtoshowmygratitude,”Pablosays.“Thisisaboutsavinglives.”CarolineFox,M.D.ispassionateaboutgenetics.Inmedicalschool,shestudiedtheeffectsoftheenvironmentondiabetesandobesityonatribeofNativeAmericans(certainpopulationsworldwidehaveagreaterpropensitytowardsdiabetes;thistribewasonesuchgroup).Herresearchlefthermotivatedtolearnmoreabouthowgeneticsplaysaroleinmetabolicdiseases.Thatwasmystart,shenotes.Sincethen,almostallofmyresearchhasbeenfocusedonuncoveringthegeneticfoundationsofthesetypesofdiseases.ChangingPerceptionsPriortojoiningMSDResearchLaboratoriesinBoston,CarolineworkedattheNationalInstitutesofHealth.There,sheledalabthatstudiedmetabolicriskfactorsforcardiovasculardiseaseaspartofthe,apioneeringlong-termpopulationstudyofcardiovasculardisease.But,shenotes,theshifttoMSDwasarelativelyeasyone.IwasimpressedbyMSDseffortstoleveragehumangeneticstodrivedrugdiscovery,shesays.Forme,itwastheperfectnextstepfromtheworkthatIhadbeendoinginacademia.Genetics:TheNewFrontierWe'relucky—CarolinespassionforgeneticsisagreatfitforMSD.Inourlabsandacrosstheindustry,weareseeinganincreaseduseofhumangeneticstohelpdeterminewhetherpatientswillrespondtoacertaindrugornot,ShepointstoMSD'sactiveresearchcollaborationswithscientistsaroundtheworldaimedatadvancingthisfieldofscience.Iamveryenthusiasticaboutwhereourresearchmaylead.

  “MyuncleIvanwasaseverediabetespatient—heneededinjectionsthreetimesaday.Hewaswithoutinsulinformorethanamonth.EvenIwasnotaware,”Pablorecounts.“Whenhefinallyreceivedinsulin,hewasinbadcondition.Severalweekslater,hishealthdeclined,hehadrenalfailure,andhedied.”ThedroneteamrecentlyacknowledgedPablo’scontributions,andhispersonalloss,bygivingtheprojectanewnickname.Oncecalled“MajorTom”aftertheDavidBowiesong,it’snow“ProjectIvan.”“Idon’thavewordsenoughtoshowmygratitude,”Pablosays.“Thisisaboutsavinglives.”CarolineFox,M.D.ispassionateaboutgenetics.Inmedicalschool,shestudiedtheeffectsoftheenvironmentondiabetesandobesityonatribeofNativeAmericans(certainpopulationsworldwidehaveagreaterpropensitytowardsdiabetes;thistribewasonesuchgroup).Herresearchlefthermotivatedtolearnmoreabouthowgeneticsplaysaroleinmetabolicdiseases.Thatwasmystart,shenotes.Sincethen,almostallofmyresearchhasbeenfocusedonuncoveringthegeneticfoundationsofthesetypesofdiseases.ChangingPerceptionsPriortojoiningMSDResearchLaboratoriesinBoston,CarolineworkedattheNationalInstitutesofHealth.There,sheledalabthatstudiedmetabolicriskfactorsforcardiovasculardiseaseaspartofthe,apioneeringlong-termpopulationstudyofcardiovasculardisease.But,shenotes,theshifttoMSDwasarelativelyeasyone.IwasimpressedbyMSDseffortstoleveragehumangeneticstodrivedrugdiscovery,shesays.Forme,itwastheperfectnextstepfromtheworkthatIhadbeendoinginacademia.Genetics:TheNewFrontierWe'relucky—CarolinespassionforgeneticsisagreatfitforMSD.Inourlabsandacrosstheindustry,weareseeinganincreaseduseofhumangeneticstohelpdeterminewhetherpatientswillrespondtoacertaindrugornot,ShepointstoMSD'sactiveresearchcollaborationswithscientistsaroundtheworldaimedatadvancingthisfieldofscience.Iamveryenthusiasticaboutwhereourresearchmaylead.In1962hercollaborators,JamesWatson,FrancisCrickandMauriceWilkinswereawardedtheNobelPrizefortheir“discoveriesconcerningthemolecularstructureofnucleicacidsanditssignificanceforinformationtransferinlivingmaterial.”Franklin’suntimelydeathdeniedhertheacclaimofthisprestigiousscientificaward(theNobelCommitteedoesnotawardtheprizeposthumously),butherroleinthisfundamentaldiscoveryhasbeenwelldocumentedandisnowwidelyrecognized.Franklin’sstoryofalifecutshortbyovariancancerremainsalltoocommon.Eventoday,advancedovariancancerremainsoneofthemostdifficultcancerstotreat.Butthereremainsareasonforoptimism.Thepaceofchangeincancertreatmenthasincreaseddramaticallyinrecentyears.Advancesinresearch–manyofwhichmaybetracedbacktoFranklin’swork–havegivenusadeeperunderstandingofhowtotargetthedisease,pavingthewayfornewdevelopments.Specifictoovariancancer,recentclinicalresearchhasshownpromiseforwomenwithadvancedstagesofthedisease.AtMSD,wearefocusedontranslatingbreakthroughscienceintooncologytherapeuticsthathavethegreatestpotentialforimprovinglong-termdiseasecontrolandsurvivalforpatients,includingthosewithovariancancer.Werecognizethatnotwopatientsorcancersarethesameandmultipleapproaches–therapeuticregimensandmechanismsofaction–willbeneededtooutpacethisdisease.That’swhywehaveworkedrigorouslytoexpandanddiversifyourowninternalresearchprograms.Thereisstillworktobedone,butwebelievestronglyinourpotentialtotransformthewayallcancersaretreated.AndweareconstantlyinspiredtoworkharderbystorieslikeRosalindFranklin’s.

  Dr.Chenghasbeentreatingheadandneckcancerpatientsformanyyears.Thisishispersonalperspective.Ihavetreatedpatientswithheadandneckcancersformanyyears,soIhaveseen,upclose,thedifficultexperienceoflivingwithheadandneckcancer.Cancerisatryingsituationforallpatientsandtheirlovedones,butheadandneckpatientsfacecancerinauniqueanddifficultway,withtheirdiseaseandtumorsoftenvisibletothepublic.Ihavebeeninvolvedinresearchforyearsaspartofscientists'decades-longendeavortobringforwardmeaningfuladvancesforpatientsdiagnosedwiththispotentiallyaggressivedisease.Untilrecently,suchadvanceswerehardtocomebyandmypatientsandIstruggledwiththelimitedtreatmentoptionsavailable.Butwhilethereisasignificantneedfornewtreatmentoptions,thegoodnewsisthattherehavebeensomeimprovementsinsurvivalratesovertheyearsandweareseeinganewandencouragingfutureahead.Wehavebeguntoleverageourunderstandingofbiologytodevelopmoreprecisetherapies.AtMSD,wearefocusedonimmuno-oncologyresearch,whichstudiestheroleoftheimmunesystemindetectingandfightingcancer.Wearestudyingthepotentialofthisapproach,whichaimstoharnessandrestorethebodysabilitytodetectandfightcancercells,inanumberofcancers,includingheadandneckcancer.Immuno-oncologyhasalreadysignificantlychangedthewaycertaincancersaretreated,includingmelanomaandlungcancer,aswellasinthetreatmentofheadandneckcancer.Changeiscomingtotheheadandneckcancerlandscape–anditisthrillingtobeapartofit.TobeabletoseehowourresearchandeffortsatMSDarehavingadirectimpactonhowphysiciansapproachthetreatmentoftheirpatientsandwhatpatientsmayexpectfromtheirtreatmentiswhatmotivatesustoworkharder.CarolineFox,M.D.ispassionateaboutgenetics.Inmedicalschool,shestudiedtheeffectsoftheenvironmentondiabetesandobesityonatribeofNativeAmericans(certainpopulationsworldwidehaveagreaterpropensitytowardsdiabetes;thistribewasonesuchgroup).Herresearchlefthermotivatedtolearnmoreabouthowgeneticsplaysaroleinmetabolicdiseases.Thatwasmystart,shenotes.Sincethen,almostallofmyresearchhasbeenfocusedonuncoveringthegeneticfoundationsofthesetypesofdiseases.ChangingPerceptionsPriortojoiningMSDResearchLaboratoriesinBoston,CarolineworkedattheNationalInstitutesofHealth.There,sheledalabthatstudiedmetabolicriskfactorsforcardiovasculardiseaseaspartofthe,apioneeringlong-termpopulationstudyofcardiovasculardisease.But,shenotes,theshifttoMSDwasarelativelyeasyone.IwasimpressedbyMSDseffortstoleveragehumangeneticstodrivedrugdiscovery,shesays.Forme,itwastheperfectnextstepfromtheworkthatIhadbeendoinginacademia.Genetics:TheNewFrontierWe'relucky—CarolinespassionforgeneticsisagreatfitforMSD.Inourlabsandacrosstheindustry,weareseeinganincreaseduseofhumangeneticstohelpdeterminewhetherpatientswillrespondtoacertaindrugornot,ShepointstoMSD'sactiveresearchcollaborationswithscientistsaroundtheworldaimedatadvancingthisfieldofscience.Iamveryenthusiasticaboutwhereourresearchmaylead.CarolineFox,M.D.ispassionateaboutgenetics.Inmedicalschool,shestudiedtheeffectsoftheenvironmentondiabetesandobesityonatribeofNativeAmericans(certainpopulationsworldwidehaveagreaterpropensitytowardsdiabetes;thistribewasonesuchgroup).Herresearchlefthermotivatedtolearnmoreabouthowgeneticsplaysaroleinmetabolicdiseases.Thatwasmystart,shenotes.Sincethen,almostallofmyresearchhasbeenfocusedonuncoveringthegeneticfoundationsofthesetypesofdiseases.ChangingPerceptionsPriortojoiningMSDResearchLaboratoriesinBoston,CarolineworkedattheNationalInstitutesofHealth.There,sheledalabthatstudiedmetabolicriskfactorsforcardiovasculardiseaseaspartofthe,apioneeringlong-termpopulationstudyofcardiovasculardisease.But,shenotes,theshifttoMSDwasarelativelyeasyone.IwasimpressedbyMSDseffortstoleveragehumangeneticstodrivedrugdiscovery,shesays.Forme,itwastheperfectnextstepfromtheworkthatIhadbeendoinginacademia.Genetics:TheNewFrontierWe'relucky—CarolinespassionforgeneticsisagreatfitforMSD.Inourlabsandacrosstheindustry,weareseeinganincreaseduseofhumangeneticstohelpdeterminewhetherpatientswillrespondtoacertaindrugornot,ShepointstoMSD'sactiveresearchcollaborationswithscientistsaroundtheworldaimedatadvancingthisfieldofscience.Iamveryenthusiasticaboutwhereourresearchmaylead.

  In1962hercollaborators,JamesWatson,FrancisCrickandMauriceWilkinswereawardedtheNobelPrizefortheir“discoveriesconcerningthemolecularstructureofnucleicacidsanditssignificanceforinformationtransferinlivingmaterial.”Franklin’suntimelydeathdeniedhertheacclaimofthisprestigiousscientificaward(theNobelCommitteedoesnotawardtheprizeposthumously),butherroleinthisfundamentaldiscoveryhasbeenwelldocumentedandisnowwidelyrecognized.Franklin’sstoryofalifecutshortbyovariancancerremainsalltoocommon.Eventoday,advancedovariancancerremainsoneofthemostdifficultcancerstotreat.Butthereremainsareasonforoptimism.Thepaceofchangeincancertreatmenthasincreaseddramaticallyinrecentyears.Advancesinresearch–manyofwhichmaybetracedbacktoFranklin’swork–havegivenusadeeperunderstandingofhowtotargetthedisease,pavingthewayfornewdevelopments.Specifictoovariancancer,recentclinicalresearchhasshownpromiseforwomenwithadvancedstagesofthedisease.AtMSD,wearefocusedontranslatingbreakthroughscienceintooncologytherapeuticsthathavethegreatestpotentialforimprovinglong-termdiseasecontrolandsurvivalforpatients,includingthosewithovariancancer.Werecognizethatnotwopatientsorcancersarethesameandmultipleapproaches–therapeuticregimensandmechanismsofaction–willbeneededtooutpacethisdisease.That’swhywehaveworkedrigorouslytoexpandanddiversifyourowninternalresearchprograms.Thereisstillworktobedone,butwebelievestronglyinourpotentialtotransformthewayallcancersaretreated.AndweareconstantlyinspiredtoworkharderbystorieslikeRosalindFranklin’s.In1962hercollaborators,JamesWatson,FrancisCrickandMauriceWilkinswereawardedtheNobelPrizefortheir“discoveriesconcerningthemolecularstructureofnucleicacidsanditssignificanceforinformationtransferinlivingmaterial.”Franklin’suntimelydeathdeniedhertheacclaimofthisprestigiousscientificaward(theNobelCommitteedoesnotawardtheprizeposthumously),butherroleinthisfundamentaldiscoveryhasbeenwelldocumentedandisnowwidelyrecognized.Franklin’sstoryofalifecutshortbyovariancancerremainsalltoocommon.Eventoday,advancedovariancancerremainsoneofthemostdifficultcancerstotreat.Butthereremainsareasonforoptimism.Thepaceofchangeincancertreatmenthasincreaseddramaticallyinrecentyears.Advancesinresearch–manyofwhichmaybetracedbacktoFranklin’swork–havegivenusadeeperunderstandingofhowtotargetthedisease,pavingthewayfornewdevelopments.Specifictoovariancancer,recentclinicalresearchhasshownpromiseforwomenwithadvancedstagesofthedisease.AtMSD,wearefocusedontranslatingbreakthroughscienceintooncologytherapeuticsthathavethegreatestpotentialforimprovinglong-termdiseasecontrolandsurvivalforpatients,includingthosewithovariancancer.Werecognizethatnotwopatientsorcancersarethesameandmultipleapproaches–therapeuticregimensandmechanismsofaction–willbeneededtooutpacethisdisease.That’swhywehaveworkedrigorouslytoexpandanddiversifyourowninternalresearchprograms.Thereisstillworktobedone,butwebelievestronglyinourpotentialtotransformthewayallcancersaretreated.AndweareconstantlyinspiredtoworkharderbystorieslikeRosalindFranklin’s.Chemistryhasbeencentraltoourbusinessofsinceourearliestdaysasacompany.Historically,ourdrugdiscoveryprocessprimarilycenteredaroundsmallmolecules.Then,thebirthofbiotechnologyinthelate1970s/early1980saddedbiologics,orengineeredproteins,tothemix.Today,newmodalitiesareemergingthatshowastrongpotentialtotargetcomplexdiseasesthathavenotyetbeenreachablewitheithersmallmoleculesorbiologics.RobGarbaccioisleadingatalentedteamofchemistswhoarehelpingguideMSD’sentryintothisexcitingnewfieldofmedicine.IntroducinganddiscoveringnewwaysforwardRobistheassociatevicepresident,ChemistryCapabilitiesforAcceleratingTherapeutics(CCAT),adiscoverychemistryteamthatislookingathowtogobeyondthetraditionalmethodsofdiscoveringanddevelopingmedicines."Therearecertaindiseasetargetsthatarereallyhardto'reach'andimpactusingtraditionalmethods,"henotes."SopartofthegroupIoverseetriestofigureouthowwecanemploynewermodalities,suchaspeptides,bioconjugates,andoligonucleotides,toaddressthechallengingtargetsthatareincreasinglyemergingfrombiologicalresearch."Rob'sgroupisnotfocusedonanyspecifictherapeuticarea--theyareseekingnewwaystoaddressthemostdifficultdiseasetargets."Inoncology,infectiousdiseases,andneuroscience,forexample,we’relookingforthosetargetsthatourcolleaguessay,'Ifonlywecouldmodulatethistarget,webelievewemightbeabletopotentiallyinterruptthediseaseprocessandhelppatients,'"henotes.Using‘creativechemistry’totreatdiseaseIt'scomplexwork,tobesure,butthat'swhatmakesitsointriguingandinspiringforRobandhisteam."ThethingthatIlikethemostaboutmyworkisthebeliefthattheremaybeapathforwardforthetreatmentofeachandeveryoneofthesediseases.Wejustcan'tseeityetbecausethebiologyissocomplex,"saysRob."Asresearcherscontinuetoimproveourunderstandingofdiseasebiology,Ibelievethatcombiningthatknowledgewithcreativechemistrywillhelpleadusdownnewroadstotreatingdiseaseandhelpingpatients."Robjoinedthecompanyaftercompletinggraduateschoolandapostdoctoralfellowshipfocusingonorganicchemistry."Icameherebecausescienceandinnovationdrivethiscompany.I'mpassionateaboutourmissiontosaveandimprovelives,andIbelievethatmybestdayatwork,thedaymyteammakesapotentiallylife-changingdiscovery,isstillaheadofme,andit'sthereasonthatIstay."InventingforlifeAtMSD,wesayweare.AndRobdefinitelyseeshimselfasaninventor."Chemistshavethisuniqueabilitytocombineatomsandbondsbetweenatomsinauniqueway.Everydaychemistsareinventinghundredsofmoleculesthathaveneverexistedbefore.So,yes,weareinventing,"hesays."Weareinventingtosolveproblems."

  Jameslikeslogicpuzzles.Andwordproblems.Luckily,hegetstoapplytheseinterestsinhisworkeveryday.Jamesisacomputationalchemist–heworkswithMSD’schemistryteams,applyingpredictivemodellingtoidentifywaystodesigndrugsandanalyzedatatohelpourscientistsprioritizethenextcompoundstomakeandtest.Althoughthesearecomplexproblemsandcomplexquestionsthatwe’retryingtosolve,wetakelogicalsteps,explainsJames.Foreveryquestion,there’sreallyananswer,yousometimesjusthavetospendalittlebitmoretimethinkingaboutit,andtakeastepbackandlookatwhat’sactuallyinfrontofyou.Bettermolecules,fasterInourgroup’sroleindrugdiscovery,wehavethismantraof‘bettermolecules,faster,saysJames.Ifachemisthas100compoundsthatshe’sthinkingaboutmaking,computationally,wecanhelpprioritizewhichonestostartwithbasedonrationaldrugdesign.Jamesenjoysbeingpartofateamworkingtoachieveasingulargoal:tocreatemedicinesthatwillhelpthepeoplewhoneedthem.And,hebelievesthatcollaborationisveryimportantforresearchanddevelopment:Youcan'tdoaprojectonyourown;youneedotherstoassistandhelp,notjustbycontributingintheirindividualrole,butalsowiththeirthinking.Jamesandhiscolleagueshavealotofexperiencewithperseveranceanddetermination,too.Ourteamsofscientistsdesign,developandscreenthousandsofcompoundsandantibodiestoultimatelyadvanceonlyafewofthemostpromisingleadcandidatesintoclinicaltesting.Moleculardesignanddevelopmentisaniterativeprocess.Youhavetostickwithit.It'scontinuouslymakingmodificationsandadaptingandevolving,eventuallygettingdowntheroadorthepipelinetomakeadrug…that'swhat'sexcitingaboutit.It’sallaboutthepatientsEveryday,IcometoworkknowingthatI’mworkingtomakeadrug.And,Idon'tknowiftodayI’mgoingtoopenupanemailwithresultssaying,‘we'veaccomplishedthisor‘weneedtochangethat.’Butregardlessofwhatthoseresultsare,it'sgoingtobeprogresstogettothatendpoint.”Ourcompanyiscommittedtodiscoveringsmart,sustainablewaystoexpandaccesstohealthcare,especiallyinareaswithlimitedinfrastructureandresources.Giventhesignificanceofthischallenge,itisonlybyworkinginpartnershipwithothers—governments,donors,patientorganizations,healthcareprofessionals,NGOs,academicinstitutions,multilateralorganizationsandtheprivatesector—thatwecanwemakethestrongestcontribution.TheMSDFellowshipforGlobalHealthisbuiltonthenotionofpartneringtostrengthenthecapacityandreachofnonprofitorganizationswhich,inturn,willultimatelysolvesomeoftheworld’sgreatesthealthcarechallenges.Historically,oncologypracticeandclinicaltrialdesignprimarilyfocusedonwherethetumorfirstemerged,suchascolonorrectum,lung,breast,andendometrium.Thisapproachfollowsthelogicofthescalpel:pinpointingthelocationofthetumorfirstenabledsurgicalplans.Morerecently,therehavebeensignificantadvancesinourunderstandingoftheroleofcancerbiomarkersinmolecularandcellularmechanismsthatcandrivetumorgrowth.Biomarkersarebiologicalmolecules(typicallycomprisedofDNA,RNAorprotein)foundintissuesorbloodthatcanserveasasigntobetterunderstandaconditionordisease.Sometimes,thesamebiomarkerisfoundacrossmanydifferenttypesofcancer,regardlessofwherethetumorfirstdeveloped.Withinaspecifictumorlocation,thesebiomarkerscansometimesdifferentiatewhetherthetumorislikelytorespondtoagiventreatment.Assuch,thesebiomarkershavebeenusedtohelpinformclinicalresearch,acceleratingtheprocessofgettingtargetedmedicinestopatientswhereseparatetrialswouldtakeyearstoconduct.Importantly,insomecases,thesefeaturescanbeassessedusinglaboratoryteststhathavelongbeenavailable.Whereatestiseithernotavailable,orforresearchuseonly,thetestmanufacturerpartnerswiththedrugmanufacturertoadvancetogetherintoregulatoryapprovalbygovernmentagencies(suchastheFDA)acompaniondiagnosticassaytoensuresafeandeffectiveuseofthedruginpatientslikelytorespond.Thegoalistouseadeeperunderstandingofthetumorbiologyandassociatedbiomarkerstotackletumorresearchmoreprecisely;goingbeyondsimplywhereatumorarose.Instead,wearelearninghowtoattackacancerbasedonitsbiologyatthecellularlevel.AtMSD,effortsareunderwaytobetterunderstandmicrosatelliteinstability(MSI)andmismatchrepairdeficiency(dMMR).Thesebiomarkersarepresentacrosstumortypes,regardlessoftheoriginallocationofthecancer.ThepresenceofhighlevelsofMSI(MSI-H)ordMMRsignifiesanunderlyingprobleminacell'sabilitytofixerrorsthatoccurwhenDNAreplicates.TumorcellsdeterminedtohaveMSI-HordMMRharborhundredstothousandsofmutations.Theultimateproofofoureffortswillmanifestasanewgenerationofcancermedicines:thosethatfollowthelogicofbiology,notthelogicofthescalpel.

  Historically,oncologypracticeandclinicaltrialdesignprimarilyfocusedonwherethetumorfirstemerged,suchascolonorrectum,lung,breast,andendometrium.Thisapproachfollowsthelogicofthescalpel:pinpointingthelocationofthetumorfirstenabledsurgicalplans.Morerecently,therehavebeensignificantadvancesinourunderstandingoftheroleofcancerbiomarkersinmolecularandcellularmechanismsthatcandrivetumorgrowth.Biomarkersarebiologicalmolecules(typicallycomprisedofDNA,RNAorprotein)foundintissuesorbloodthatcanserveasasigntobetterunderstandaconditionordisease.Sometimes,thesamebiomarkerisfoundacrossmanydifferenttypesofcancer,regardlessofwherethetumorfirstdeveloped.Withinaspecifictumorlocation,thesebiomarkerscansometimesdifferentiatewhetherthetumorislikelytorespondtoagiventreatment.Assuch,thesebiomarkershavebeenusedtohelpinformclinicalresearch,acceleratingtheprocessofgettingtargetedmedicinestopatientswhereseparatetrialswouldtakeyearstoconduct.Importantly,insomecases,thesefeaturescanbeassessedusinglaboratoryteststhathavelongbeenavailable.Whereatestiseithernotavailable,orforresearchuseonly,thetestmanufacturerpartnerswiththedrugmanufacturertoadvancetogetherintoregulatoryapprovalbygovernmentagencies(suchastheFDA)acompaniondiagnosticassaytoensuresafeandeffectiveuseofthedruginpatientslikelytorespond.Thegoalistouseadeeperunderstandingofthetumorbiologyandassociatedbiomarkerstotackletumorresearchmoreprecisely;goingbeyondsimplywhereatumorarose.Instead,wearelearninghowtoattackacancerbasedonitsbiologyatthecellularlevel.AtMSD,effortsareunderwaytobetterunderstandmicrosatelliteinstability(MSI)andmismatchrepairdeficiency(dMMR).Thesebiomarkersarepresentacrosstumortypes,regardlessoftheoriginallocationofthecancer.ThepresenceofhighlevelsofMSI(MSI-H)ordMMRsignifiesanunderlyingprobleminacell'sabilitytofixerrorsthatoccurwhenDNAreplicates.TumorcellsdeterminedtohaveMSI-HordMMRharborhundredstothousandsofmutations.Theultimateproofofoureffortswillmanifestasanewgenerationofcancermedicines:thosethatfollowthelogicofbiology,notthelogicofthescalpel.Jameslikeslogicpuzzles.Andwordproblems.Luckily,hegetstoapplytheseinterestsinhisworkeveryday.Jamesisacomputationalchemist–heworkswithMSD’schemistryteams,applyingpredictivemodellingtoidentifywaystodesigndrugsandanalyzedatatohelpourscientistsprioritizethenextcompoundstomakeandtest.Althoughthesearecomplexproblemsandcomplexquestionsthatwe’retryingtosolve,wetakelogicalsteps,explainsJames.Foreveryquestion,there’sreallyananswer,yousometimesjusthavetospendalittlebitmoretimethinkingaboutit,andtakeastepbackandlookatwhat’sactuallyinfrontofyou.Bettermolecules,fasterInourgroup’sroleindrugdiscovery,wehavethismantraof‘bettermolecules,faster,saysJames.Ifachemisthas100compoundsthatshe’sthinkingaboutmaking,computationally,wecanhelpprioritizewhichonestostartwithbasedonrationaldrugdesign.Jamesenjoysbeingpartofateamworkingtoachieveasingulargoal:tocreatemedicinesthatwillhelpthepeoplewhoneedthem.And,hebelievesthatcollaborationisveryimportantforresearchanddevelopment:Youcan'tdoaprojectonyourown;youneedotherstoassistandhelp,notjustbycontributingintheirindividualrole,butalsowiththeirthinking.Jamesandhiscolleagueshavealotofexperiencewithperseveranceanddetermination,too.Ourteamsofscientistsdesign,developandscreenthousandsofcompoundsandantibodiestoultimatelyadvanceonlyafewofthemostpromisingleadcandidatesintoclinicaltesting.Moleculardesignanddevelopmentisaniterativeprocess.Youhavetostickwithit.It'scontinuouslymakingmodificationsandadaptingandevolving,eventuallygettingdowntheroadorthepipelinetomakeadrug…that'swhat'sexcitingaboutit.It’sallaboutthepatientsEveryday,IcometoworkknowingthatI’mworkingtomakeadrug.And,Idon'tknowiftodayI’mgoingtoopenupanemailwithresultssaying,‘we'veaccomplishedthisor‘weneedtochangethat.’Butregardlessofwhatthoseresultsare,it'sgoingtobeprogresstogettothatendpoint.”Historically,oncologypracticeandclinicaltrialdesignprimarilyfocusedonwherethetumorfirstemerged,suchascolonorrectum,lung,breast,andendometrium.Thisapproachfollowsthelogicofthescalpel:pinpointingthelocationofthetumorfirstenabledsurgicalplans.Morerecently,therehavebeensignificantadvancesinourunderstandingoftheroleofcancerbiomarkersinmolecularandcellularmechanismsthatcandrivetumorgrowth.Biomarkersarebiologicalmolecules(typicallycomprisedofDNA,RNAorprotein)foundintissuesorbloodthatcanserveasasigntobetterunderstandaconditionordisease.Sometimes,thesamebiomarkerisfoundacrossmanydifferenttypesofcancer,regardlessofwherethetumorfirstdeveloped.Withinaspecifictumorlocation,thesebiomarkerscansometimesdifferentiatewhetherthetumorislikelytorespondtoagiventreatment.Assuch,thesebiomarkershavebeenusedtohelpinformclinicalresearch,acceleratingtheprocessofgettingtargetedmedicinestopatientswhereseparatetrialswouldtakeyearstoconduct.Importantly,insomecases,thesefeaturescanbeassessedusinglaboratoryteststhathavelongbeenavailable.Whereatestiseithernotavailable,orforresearchuseonly,thetestmanufacturerpartnerswiththedrugmanufacturertoadvancetogetherintoregulatoryapprovalbygovernmentagencies(suchastheFDA)acompaniondiagnosticassaytoensuresafeandeffectiveuseofthedruginpatientslikelytorespond.Thegoalistouseadeeperunderstandingofthetumorbiologyandassociatedbiomarkerstotackletumorresearchmoreprecisely;goingbeyondsimplywhereatumorarose.Instead,wearelearninghowtoattackacancerbasedonitsbiologyatthecellularlevel.AtMSD,effortsareunderwaytobetterunderstandmicrosatelliteinstability(MSI)andmismatchrepairdeficiency(dMMR).Thesebiomarkersarepresentacrosstumortypes,regardlessoftheoriginallocationofthecancer.ThepresenceofhighlevelsofMSI(MSI-H)ordMMRsignifiesanunderlyingprobleminacell'sabilitytofixerrorsthatoccurwhenDNAreplicates.TumorcellsdeterminedtohaveMSI-HordMMRharborhundredstothousandsofmutations.Theultimateproofofoureffortswillmanifestasanewgenerationofcancermedicines:thosethatfollowthelogicofbiology,notthelogicofthescalpel.

  CarolineFox,M.D.ispassionateaboutgenetics.Inmedicalschool,shestudiedtheeffectsoftheenvironmentondiabetesandobesityonatribeofNativeAmericans(certainpopulationsworldwidehaveagreaterpropensitytowardsdiabetes;thistribewasonesuchgroup).Herresearchlefthermotivatedtolearnmoreabouthowgeneticsplaysaroleinmetabolicdiseases.Thatwasmystart,shenotes.Sincethen,almostallofmyresearchhasbeenfocusedonuncoveringthegeneticfoundationsofthesetypesofdiseases.ChangingPerceptionsPriortojoiningMSDResearchLaboratoriesinBoston,CarolineworkedattheNationalInstitutesofHealth.There,sheledalabthatstudiedmetabolicriskfactorsforcardiovasculardiseaseaspartofthe,apioneeringlong-termpopulationstudyofcardiovasculardisease.But,shenotes,theshifttoMSDwasarelativelyeasyone.IwasimpressedbyMSDseffortstoleveragehumangeneticstodrivedrugdiscovery,shesays.Forme,itwastheperfectnextstepfromtheworkthatIhadbeendoinginacademia.Genetics:TheNewFrontierWe'relucky—CarolinespassionforgeneticsisagreatfitforMSD.Inourlabsandacrosstheindustry,weareseeinganincreaseduseofhumangeneticstohelpdeterminewhetherpatientswillrespondtoacertaindrugornot,ShepointstoMSD'sactiveresearchcollaborationswithscientistsaroundtheworldaimedatadvancingthisfieldofscience.Iamveryenthusiasticaboutwhereourresearchmaylead.In1962hercollaborators,JamesWatson,FrancisCrickandMauriceWilkinswereawardedtheNobelPrizefortheir“discoveriesconcerningthemolecularstructureofnucleicacidsanditssignificanceforinformationtransferinlivingmaterial.”Franklin’suntimelydeathdeniedhertheacclaimofthisprestigiousscientificaward(theNobelCommitteedoesnotawardtheprizeposthumously),butherroleinthisfundamentaldiscoveryhasbeenwelldocumentedandisnowwidelyrecognized.Franklin’sstoryofalifecutshortbyovariancancerremainsalltoocommon.Eventoday,advancedovariancancerremainsoneofthemostdifficultcancerstotreat.Butthereremainsareasonforoptimism.Thepaceofchangeincancertreatmenthasincreaseddramaticallyinrecentyears.Advancesinresearch–manyofwhichmaybetracedbacktoFranklin’swork–havegivenusadeeperunderstandingofhowtotargetthedisease,pavingthewayfornewdevelopments.Specifictoovariancancer,recentclinicalresearchhasshownpromiseforwomenwithadvancedstagesofthedisease.AtMSD,wearefocusedontranslatingbreakthroughscienceintooncologytherapeuticsthathavethegreatestpotentialforimprovinglong-termdiseasecontrolandsurvivalforpatients,includingthosewithovariancancer.Werecognizethatnotwopatientsorcancersarethesameandmultipleapproaches–therapeuticregimensandmechanismsofaction–willbeneededtooutpacethisdisease.That’swhywehaveworkedrigorouslytoexpandanddiversifyourowninternalresearchprograms.Thereisstillworktobedone,butwebelievestronglyinourpotentialtotransformthewayallcancersaretreated.AndweareconstantlyinspiredtoworkharderbystorieslikeRosalindFranklin’s.“MyuncleIvanwasaseverediabetespatient—heneededinjectionsthreetimesaday.Hewaswithoutinsulinformorethanamonth.EvenIwasnotaware,”Pablorecounts.“Whenhefinallyreceivedinsulin,hewasinbadcondition.Severalweekslater,hishealthdeclined,hehadrenalfailure,andhedied.”ThedroneteamrecentlyacknowledgedPablo’scontributions,andhispersonalloss,bygivingtheprojectanewnickname.Oncecalled“MajorTom”aftertheDavidBowiesong,it’snow“ProjectIvan.”“Idon’thavewordsenoughtoshowmygratitude,”Pablosays.“Thisisaboutsavinglives.”

  In1962hercollaborators,JamesWatson,FrancisCrickandMauriceWilkinswereawardedtheNobelPrizefortheir“discoveriesconcerningthemolecularstructureofnucleicacidsanditssignificanceforinformationtransferinlivingmaterial.”Franklin’suntimelydeathdeniedhertheacclaimofthisprestigiousscientificaward(theNobelCommitteedoesnotawardtheprizeposthumously),butherroleinthisfundamentaldiscoveryhasbeenwelldocumentedandisnowwidelyrecognized.Franklin’sstoryofalifecutshortbyovariancancerremainsalltoocommon.Eventoday,advancedovariancancerremainsoneofthemostdifficultcancerstotreat.Butthereremainsareasonforoptimism.Thepaceofchangeincancertreatmenthasincreaseddramaticallyinrecentyears.Advancesinresearch–manyofwhichmaybetracedbacktoFranklin’swork–havegivenusadeeperunderstandingofhowtotargetthedisease,pavingthewayfornewdevelopments.Specifictoovariancancer,recentclinicalresearchhasshownpromiseforwomenwithadvancedstagesofthedisease.AtMSD,wearefocusedontranslatingbreakthroughscienceintooncologytherapeuticsthathavethegreatestpotentialforimprovinglong-termdiseasecontrolandsurvivalforpatients,includingthosewithovariancancer.Werecognizethatnotwopatientsorcancersarethesameandmultipleapproaches–therapeuticregimensandmechanismsofaction–willbeneededtooutpacethisdisease.That’swhywehaveworkedrigorouslytoexpandanddiversifyourowninternalresearchprograms.Thereisstillworktobedone,butwebelievestronglyinourpotentialtotransformthewayallcancersaretreated.AndweareconstantlyinspiredtoworkharderbystorieslikeRosalindFranklin’s.Ourcompanyiscommittedtodiscoveringsmart,sustainablewaystoexpandaccesstohealthcare,especiallyinareaswithlimitedinfrastructureandresources.Giventhesignificanceofthischallenge,itisonlybyworkinginpartnershipwithothers—governments,donors,patientorganizations,healthcareprofessionals,NGOs,academicinstitutions,multilateralorganizationsandtheprivatesector—thatwecanwemakethestrongestcontribution.TheMSDFellowshipforGlobalHealthisbuiltonthenotionofpartneringtostrengthenthecapacityandreachofnonprofitorganizationswhich,inturn,willultimatelysolvesomeoftheworld’sgreatesthealthcarechallenges.Ourcompanyiscommittedtodiscoveringsmart,sustainablewaystoexpandaccesstohealthcare,especiallyinareaswithlimitedinfrastructureandresources.Giventhesignificanceofthischallenge,itisonlybyworkinginpartnershipwithothers—governments,donors,patientorganizations,healthcareprofessionals,NGOs,academicinstitutions,multilateralorganizationsandtheprivatesector—thatwecanwemakethestrongestcontribution.TheMSDFellowshipforGlobalHealthisbuiltonthenotionofpartneringtostrengthenthecapacityandreachofnonprofitorganizationswhich,inturn,willultimatelysolvesomeoftheworld’sgreatesthealthcarechallenges.

  Toexpressourappreciation,MSDbegan#DearCancerHeroes–asocialmediacampaigntorecognizetheirfortitudeandcontributionstothefield.It’sasmallgesturetoshowourgratitude.Wewanttoletclinicaltrialparticipantsknowtheyarenotaloneandthereisawholecommunityofpeoplecheeringthemon.Anyonecanjointhemovementbywritingamessagetocancerclinicaltrialparticipantsonastickynoteandsharingitonsocialmediausing#DearCancerHeroes.Cancerresearchhascomealongwayandstillhasalongwaytogo.However,wewouldn’thavegottentowherewearetodaywithouttheseheroes.Dr.Chenghasbeentreatingheadandneckcancerpatientsformanyyears.Thisishispersonalperspective.Ihavetreatedpatientswithheadandneckcancersformanyyears,soIhaveseen,upclose,thedifficultexperienceoflivingwithheadandneckcancer.Cancerisatryingsituationforallpatientsandtheirlovedones,butheadandneckpatientsfacecancerinauniqueanddifficultway,withtheirdiseaseandtumorsoftenvisibletothepublic.Ihavebeeninvolvedinresearchforyearsaspartofscientists'decades-longendeavortobringforwardmeaningfuladvancesforpatientsdiagnosedwiththispotentiallyaggressivedisease.Untilrecently,suchadvanceswerehardtocomebyandmypatientsandIstruggledwiththelimitedtreatmentoptionsavailable.Butwhilethereisasignificantneedfornewtreatmentoptions,thegoodnewsisthattherehavebeensomeimprovementsinsurvivalratesovertheyearsandweareseeinganewandencouragingfutureahead.Wehavebeguntoleverageourunderstandingofbiologytodevelopmoreprecisetherapies.AtMSD,wearefocusedonimmuno-oncologyresearch,whichstudiestheroleoftheimmunesystemindetectingandfightingcancer.Wearestudyingthepotentialofthisapproach,whichaimstoharnessandrestorethebodysabilitytodetectandfightcancercells,inanumberofcancers,includingheadandneckcancer.Immuno-oncologyhasalreadysignificantlychangedthewaycertaincancersaretreated,includingmelanomaandlungcancer,aswellasinthetreatmentofheadandneckcancer.Changeiscomingtotheheadandneckcancerlandscape–anditisthrillingtobeapartofit.TobeabletoseehowourresearchandeffortsatMSDarehavingadirectimpactonhowphysiciansapproachthetreatmentoftheirpatientsandwhatpatientsmayexpectfromtheirtreatmentiswhatmotivatesustoworkharder.Dr.Chenghasbeentreatingheadandneckcancerpatientsformanyyears.Thisishispersonalperspective.Ihavetreatedpatientswithheadandneckcancersformanyyears,soIhaveseen,upclose,thedifficultexperienceoflivingwithheadandneckcancer.Cancerisatryingsituationforallpatientsandtheirlovedones,butheadandneckpatientsfacecancerinauniqueanddifficultway,withtheirdiseaseandtumorsoftenvisibletothepublic.Ihavebeeninvolvedinresearchforyearsaspartofscientists'decades-longendeavortobringforwardmeaningfuladvancesforpatientsdiagnosedwiththispotentiallyaggressivedisease.Untilrecently,suchadvanceswerehardtocomebyandmypatientsandIstruggledwiththelimitedtreatmentoptionsavailable.Butwhilethereisasignificantneedfornewtreatmentoptions,thegoodnewsisthattherehavebeensomeimprovementsinsurvivalratesovertheyearsandweareseeinganewandencouragingfutureahead.Wehavebeguntoleverageourunderstandingofbiologytodevelopmoreprecisetherapies.AtMSD,wearefocusedonimmuno-oncologyresearch,whichstudiestheroleoftheimmunesystemindetectingandfightingcancer.Wearestudyingthepotentialofthisapproach,whichaimstoharnessandrestorethebodysabilitytodetectandfightcancercells,inanumberofcancers,includingheadandneckcancer.Immuno-oncologyhasalreadysignificantlychangedthewaycertaincancersaretreated,includingmelanomaandlungcancer,aswellasinthetreatmentofheadandneckcancer.Changeiscomingtotheheadandneckcancerlandscape–anditisthrillingtobeapartofit.TobeabletoseehowourresearchandeffortsatMSDarehavingadirectimpactonhowphysiciansapproachthetreatmentoftheirpatientsandwhatpatientsmayexpectfromtheirtreatmentiswhatmotivatesustoworkharder.

  In1962hercollaborators,JamesWatson,FrancisCrickandMauriceWilkinswereawardedtheNobelPrizefortheir“discoveriesconcerningthemolecularstructureofnucleicacidsanditssignificanceforinformationtransferinlivingmaterial.”Franklin’suntimelydeathdeniedhertheacclaimofthisprestigiousscientificaward(theNobelCommitteedoesnotawardtheprizeposthumously),butherroleinthisfundamentaldiscoveryhasbeenwelldocumentedandisnowwidelyrecognized.Franklin’sstoryofalifecutshortbyovariancancerremainsalltoocommon.Eventoday,advancedovariancancerremainsoneofthemostdifficultcancerstotreat.Butthereremainsareasonforoptimism.Thepaceofchangeincancertreatmenthasincreaseddramaticallyinrecentyears.Advancesinresearch–manyofwhichmaybetracedbacktoFranklin’swork–havegivenusadeeperunderstandingofhowtotargetthedisease,pavingthewayfornewdevelopments.Specifictoovariancancer,recentclinicalresearchhasshownpromiseforwomenwithadvancedstagesofthedisease.AtMSD,wearefocusedontranslatingbreakthroughscienceintooncologytherapeuticsthathavethegreatestpotentialforimprovinglong-termdiseasecontrolandsurvivalforpatients,includingthosewithovariancancer.Werecognizethatnotwopatientsorcancersarethesameandmultipleapproaches–therapeuticregimensandmechanismsofaction–willbeneededtooutpacethisdisease.That’swhywehaveworkedrigorouslytoexpandanddiversifyourowninternalresearchprograms.Thereisstillworktobedone,butwebelievestronglyinourpotentialtotransformthewayallcancersaretreated.AndweareconstantlyinspiredtoworkharderbystorieslikeRosalindFranklin’s.Toexpressourappreciation,MSDbegan#DearCancerHeroes–asocialmediacampaigntorecognizetheirfortitudeandcontributionstothefield.It’sasmallgesturetoshowourgratitude.Wewanttoletclinicaltrialparticipantsknowtheyarenotaloneandthereisawholecommunityofpeoplecheeringthemon.Anyonecanjointhemovementbywritingamessagetocancerclinicaltrialparticipantsonastickynoteandsharingitonsocialmediausing#DearCancerHeroes.Cancerresearchhascomealongwayandstillhasalongwaytogo.However,wewouldn’thavegottentowherewearetodaywithouttheseheroes.“MyuncleIvanwasaseverediabetespatient—heneededinjectionsthreetimesaday.Hewaswithoutinsulinformorethanamonth.EvenIwasnotaware,”Pablorecounts.“Whenhefinallyreceivedinsulin,hewasinbadcondition.Severalweekslater,hishealthdeclined,hehadrenalfailure,andhedied.”ThedroneteamrecentlyacknowledgedPablo’scontributions,andhispersonalloss,bygivingtheprojectanewnickname.Oncecalled“MajorTom”aftertheDavidBowiesong,it’snow“ProjectIvan.”“Idon’thavewordsenoughtoshowmygratitude,”Pablosays.“Thisisaboutsavinglives.”

  Historically,oncologypracticeandclinicaltrialdesignprimarilyfocusedonwherethetumorfirstemerged,suchascolonorrectum,lung,breast,andendometrium.Thisapproachfollowsthelogicofthescalpel:pinpointingthelocationofthetumorfirstenabledsurgicalplans.Morerecently,therehavebeensignificantadvancesinourunderstandingoftheroleofcancerbiomarkersinmolecularandcellularmechanismsthatcandrivetumorgrowth.Biomarkersarebiologicalmolecules(typicallycomprisedofDNA,RNAorprotein)foundintissuesorbloodthatcanserveasasigntobetterunderstandaconditionordisease.Sometimes,thesamebiomarkerisfoundacrossmanydifferenttypesofcancer,regardlessofwherethetumorfirstdeveloped.Withinaspecifictumorlocation,thesebiomarkerscansometimesdifferentiatewhetherthetumorislikelytorespondtoagiventreatment.Assuch,thesebiomarkershavebeenusedtohelpinformclinicalresearch,acceleratingtheprocessofgettingtargetedmedicinestopatientswhereseparatetrialswouldtakeyearstoconduct.Importantly,insomecases,thesefeaturescanbeassessedusinglaboratoryteststhathavelongbeenavailable.Whereatestiseithernotavailable,orforresearchuseonly,thetestmanufacturerpartnerswiththedrugmanufacturertoadvancetogetherintoregulatoryapprovalbygovernmentagencies(suchastheFDA)acompaniondiagnosticassaytoensuresafeandeffectiveuseofthedruginpatientslikelytorespond.Thegoalistouseadeeperunderstandingofthetumorbiologyandassociatedbiomarkerstotackletumorresearchmoreprecisely;goingbeyondsimplywhereatumorarose.Instead,wearelearninghowtoattackacancerbasedonitsbiologyatthecellularlevel.AtMSD,effortsareunderwaytobetterunderstandmicrosatelliteinstability(MSI)andmismatchrepairdeficiency(dMMR).Thesebiomarkersarepresentacrosstumortypes,regardlessoftheoriginallocationofthecancer.ThepresenceofhighlevelsofMSI(MSI-H)ordMMRsignifiesanunderlyingprobleminacell'sabilitytofixerrorsthatoccurwhenDNAreplicates.TumorcellsdeterminedtohaveMSI-HordMMRharborhundredstothousandsofmutations.Theultimateproofofoureffortswillmanifestasanewgenerationofcancermedicines:thosethatfollowthelogicofbiology,notthelogicofthescalpel.Ourcompanyiscommittedtodiscoveringsmart,sustainablewaystoexpandaccesstohealthcare,especiallyinareaswithlimitedinfrastructureandresources.Giventhesignificanceofthischallenge,itisonlybyworkinginpartnershipwithothers—governments,donors,patientorganizations,healthcareprofessionals,NGOs,academicinstitutions,multilateralorganizationsandtheprivatesector—thatwecanwemakethestrongestcontribution.TheMSDFellowshipforGlobalHealthisbuiltonthenotionofpartneringtostrengthenthecapacityandreachofnonprofitorganizationswhich,inturn,willultimatelysolvesomeoftheworld’sgreatesthealthcarechallenges.Chemistryhasbeencentraltoourbusinessofsinceourearliestdaysasacompany.Historically,ourdrugdiscoveryprocessprimarilycenteredaroundsmallmolecules.Then,thebirthofbiotechnologyinthelate1970s/early1980saddedbiologics,orengineeredproteins,tothemix.Today,newmodalitiesareemergingthatshowastrongpotentialtotargetcomplexdiseasesthathavenotyetbeenreachablewitheithersmallmoleculesorbiologics.RobGarbaccioisleadingatalentedteamofchemistswhoarehelpingguideMSD’sentryintothisexcitingnewfieldofmedicine.IntroducinganddiscoveringnewwaysforwardRobistheassociatevicepresident,ChemistryCapabilitiesforAcceleratingTherapeutics(CCAT),adiscoverychemistryteamthatislookingathowtogobeyondthetraditionalmethodsofdiscoveringanddevelopingmedicines."Therearecertaindiseasetargetsthatarereallyhardto'reach'andimpactusingtraditionalmethods,"henotes."SopartofthegroupIoverseetriestofigureouthowwecanemploynewermodalities,suchaspeptides,bioconjugates,andoligonucleotides,toaddressthechallengingtargetsthatareincreasinglyemergingfrombiologicalresearch."Rob'sgroupisnotfocusedonanyspecifictherapeuticarea--theyareseekingnewwaystoaddressthemostdifficultdiseasetargets."Inoncology,infectiousdiseases,andneuroscience,forexample,we’relookingforthosetargetsthatourcolleaguessay,'Ifonlywecouldmodulatethistarget,webelievewemightbeabletopotentiallyinterruptthediseaseprocessandhelppatients,'"henotes.Using‘creativechemistry’totreatdiseaseIt'scomplexwork,tobesure,butthat'swhatmakesitsointriguingandinspiringforRobandhisteam."ThethingthatIlikethemostaboutmyworkisthebeliefthattheremaybeapathforwardforthetreatmentofeachandeveryoneofthesediseases.Wejustcan'tseeityetbecausethebiologyissocomplex,"saysRob."Asresearcherscontinuetoimproveourunderstandingofdiseasebiology,Ibelievethatcombiningthatknowledgewithcreativechemistrywillhelpleadusdownnewroadstotreatingdiseaseandhelpingpatients."Robjoinedthecompanyaftercompletinggraduateschoolandapostdoctoralfellowshipfocusingonorganicchemistry."Icameherebecausescienceandinnovationdrivethiscompany.I'mpassionateaboutourmissiontosaveandimprovelives,andIbelievethatmybestdayatwork,thedaymyteammakesapotentiallylife-changingdiscovery,isstillaheadofme,andit'sthereasonthatIstay."InventingforlifeAtMSD,wesayweare.AndRobdefinitelyseeshimselfasaninventor."Chemistshavethisuniqueabilitytocombineatomsandbondsbetweenatomsinauniqueway.Everydaychemistsareinventinghundredsofmoleculesthathaveneverexistedbefore.So,yes,weareinventing,"hesays."Weareinventingtosolveproblems."

  “MyuncleIvanwasaseverediabetespatient—heneededinjectionsthreetimesaday.Hewaswithoutinsulinformorethanamonth.EvenIwasnotaware,”Pablorecounts.“Whenhefinallyreceivedinsulin,hewasinbadcondition.Severalweekslater,hishealthdeclined,hehadrenalfailure,andhedied.”ThedroneteamrecentlyacknowledgedPablo’scontributions,andhispersonalloss,bygivingtheprojectanewnickname.Oncecalled“MajorTom”aftertheDavidBowiesong,it’snow“ProjectIvan.”“Idon’thavewordsenoughtoshowmygratitude,”Pablosays.“Thisisaboutsavinglives.”In1962hercollaborators,JamesWatson,FrancisCrickandMauriceWilkinswereawardedtheNobelPrizefortheir“discoveriesconcerningthemolecularstructureofnucleicacidsanditssignificanceforinformationtransferinlivingmaterial.”Franklin’suntimelydeathdeniedhertheacclaimofthisprestigiousscientificaward(theNobelCommitteedoesnotawardtheprizeposthumously),butherroleinthisfundamentaldiscoveryhasbeenwelldocumentedandisnowwidelyrecognized.Franklin’sstoryofalifecutshortbyovariancancerremainsalltoocommon.Eventoday,advancedovariancancerremainsoneofthemostdifficultcancerstotreat.Butthereremainsareasonforoptimism.Thepaceofchangeincancertreatmenthasincreaseddramaticallyinrecentyears.Advancesinresearch–manyofwhichmaybetracedbacktoFranklin’swork–havegivenusadeeperunderstandingofhowtotargetthedisease,pavingthewayfornewdevelopments.Specifictoovariancancer,recentclinicalresearchhasshownpromiseforwomenwithadvancedstagesofthedisease.AtMSD,wearefocusedontranslatingbreakthroughscienceintooncologytherapeuticsthathavethegreatestpotentialforimprovinglong-termdiseasecontrolandsurvivalforpatients,includingthosewithovariancancer.Werecognizethatnotwopatientsorcancersarethesameandmultipleapproaches–therapeuticregimensandmechanismsofaction–willbeneededtooutpacethisdisease.That’swhywehaveworkedrigorouslytoexpandanddiversifyourowninternalresearchprograms.Thereisstillworktobedone,butwebelievestronglyinourpotentialtotransformthewayallcancersaretreated.AndweareconstantlyinspiredtoworkharderbystorieslikeRosalindFranklin’s.CarolineFox,M.D.ispassionateaboutgenetics.Inmedicalschool,shestudiedtheeffectsoftheenvironmentondiabetesandobesityonatribeofNativeAmericans(certainpopulationsworldwidehaveagreaterpropensitytowardsdiabetes;thistribewasonesuchgroup).Herresearchlefthermotivatedtolearnmoreabouthowgeneticsplaysaroleinmetabolicdiseases.Thatwasmystart,shenotes.Sincethen,almostallofmyresearchhasbeenfocusedonuncoveringthegeneticfoundationsofthesetypesofdiseases.ChangingPerceptionsPriortojoiningMSDResearchLaboratoriesinBoston,CarolineworkedattheNationalInstitutesofHealth.There,sheledalabthatstudiedmetabolicriskfactorsforcardiovasculardiseaseaspartofthe,apioneeringlong-termpopulationstudyofcardiovasculardisease.But,shenotes,theshifttoMSDwasarelativelyeasyone.IwasimpressedbyMSDseffortstoleveragehumangeneticstodrivedrugdiscovery,shesays.Forme,itwastheperfectnextstepfromtheworkthatIhadbeendoinginacademia.Genetics:TheNewFrontierWe'relucky—CarolinespassionforgeneticsisagreatfitforMSD.Inourlabsandacrosstheindustry,weareseeinganincreaseduseofhumangeneticstohelpdeterminewhetherpatientswillrespondtoacertaindrugornot,ShepointstoMSD'sactiveresearchcollaborationswithscientistsaroundtheworldaimedatadvancingthisfieldofscience.Iamveryenthusiasticaboutwhereourresearchmaylead.

  Chemistryhasbeencentraltoourbusinessofsinceourearliestdaysasacompany.Historically,ourdrugdiscoveryprocessprimarilycenteredaroundsmallmolecules.Then,thebirthofbiotechnologyinthelate1970s/early1980saddedbiologics,orengineeredproteins,tothemix.Today,newmodalitiesareemergingthatshowastrongpotentialtotargetcomplexdiseasesthathavenotyetbeenreachablewitheithersmallmoleculesorbiologics.RobGarbaccioisleadingatalentedteamofchemistswhoarehelpingguideMSD’sentryintothisexcitingnewfieldofmedicine.IntroducinganddiscoveringnewwaysforwardRobistheassociatevicepresident,ChemistryCapabilitiesforAcceleratingTherapeutics(CCAT),adiscoverychemistryteamthatislookingathowtogobeyondthetraditionalmethodsofdiscoveringanddevelopingmedicines."Therearecertaindiseasetargetsthatarereallyhardto'reach'andimpactusingtraditionalmethods,"henotes."SopartofthegroupIoverseetriestofigureouthowwecanemploynewermodalities,suchaspeptides,bioconjugates,andoligonucleotides,toaddressthechallengingtargetsthatareincreasinglyemergingfrombiologicalresearch."Rob'sgroupisnotfocusedonanyspecifictherapeuticarea--theyareseekingnewwaystoaddressthemostdifficultdiseasetargets."Inoncology,infectiousdiseases,andneuroscience,forexample,we’relookingforthosetargetsthatourcolleaguessay,'Ifonlywecouldmodulatethistarget,webelievewemightbeabletopotentiallyinterruptthediseaseprocessandhelppatients,'"henotes.Using‘creativechemistry’totreatdiseaseIt'scomplexwork,tobesure,butthat'swhatmakesitsointriguingandinspiringforRobandhisteam."ThethingthatIlikethemostaboutmyworkisthebeliefthattheremaybeapathforwardforthetreatmentofeachandeveryoneofthesediseases.Wejustcan'tseeityetbecausethebiologyissocomplex,"saysRob."Asresearcherscontinuetoimproveourunderstandingofdiseasebiology,Ibelievethatcombiningthatknowledgewithcreativechemistrywillhelpleadusdownnewroadstotreatingdiseaseandhelpingpatients."Robjoinedthecompanyaftercompletinggraduateschoolandapostdoctoralfellowshipfocusingonorganicchemistry."Icameherebecausescienceandinnovationdrivethiscompany.I'mpassionateaboutourmissiontosaveandimprovelives,andIbelievethatmybestdayatwork,thedaymyteammakesapotentiallylife-changingdiscovery,isstillaheadofme,andit'sthereasonthatIstay."InventingforlifeAtMSD,wesayweare.AndRobdefinitelyseeshimselfasaninventor."Chemistshavethisuniqueabilitytocombineatomsandbondsbetweenatomsinauniqueway.Everydaychemistsareinventinghundredsofmoleculesthathaveneverexistedbefore.So,yes,weareinventing,"hesays."Weareinventingtosolveproblems."Historically,oncologypracticeandclinicaltrialdesignprimarilyfocusedonwherethetumorfirstemerged,suchascolonorrectum,lung,breast,andendometrium.Thisapproachfollowsthelogicofthescalpel:pinpointingthelocationofthetumorfirstenabledsurgicalplans.Morerecently,therehavebeensignificantadvancesinourunderstandingoftheroleofcancerbiomarkersinmolecularandcellularmechanismsthatcandrivetumorgrowth.Biomarkersarebiologicalmolecules(typicallycomprisedofDNA,RNAorprotein)foundintissuesorbloodthatcanserveasasigntobetterunderstandaconditionordisease.Sometimes,thesamebiomarkerisfoundacrossmanydifferenttypesofcancer,regardlessofwherethetumorfirstdeveloped.Withinaspecifictumorlocation,thesebiomarkerscansometimesdifferentiatewhetherthetumorislikelytorespondtoagiventreatment.Assuch,thesebiomarkershavebeenusedtohelpinformclinicalresearch,acceleratingtheprocessofgettingtargetedmedicinestopatientswhereseparatetrialswouldtakeyearstoconduct.Importantly,insomecases,thesefeaturescanbeassessedusinglaboratoryteststhathavelongbeenavailable.Whereatestiseithernotavailable,orforresearchuseonly,thetestmanufacturerpartnerswiththedrugmanufacturertoadvancetogetherintoregulatoryapprovalbygovernmentagencies(suchastheFDA)acompaniondiagnosticassaytoensuresafeandeffectiveuseofthedruginpatientslikelytorespond.Thegoalistouseadeeperunderstandingofthetumorbiologyandassociatedbiomarkerstotackletumorresearchmoreprecisely;goingbeyondsimplywhereatumorarose.Instead,wearelearninghowtoattackacancerbasedonitsbiologyatthecellularlevel.AtMSD,effortsareunderwaytobetterunderstandmicrosatelliteinstability(MSI)andmismatchrepairdeficiency(dMMR).Thesebiomarkersarepresentacrosstumortypes,regardlessoftheoriginallocationofthecancer.ThepresenceofhighlevelsofMSI(MSI-H)ordMMRsignifiesanunderlyingprobleminacell'sabilitytofixerrorsthatoccurwhenDNAreplicates.TumorcellsdeterminedtohaveMSI-HordMMRharborhundredstothousandsofmutations.Theultimateproofofoureffortswillmanifestasanewgenerationofcancermedicines:thosethatfollowthelogicofbiology,notthelogicofthescalpel.Dr.Chenghasbeentreatingheadandneckcancerpatientsformanyyears.Thisishispersonalperspective.Ihavetreatedpatientswithheadandneckcancersformanyyears,soIhaveseen,upclose,thedifficultexperienceoflivingwithheadandneckcancer.Cancerisatryingsituationforallpatientsandtheirlovedones,butheadandneckpatientsfacecancerinauniqueanddifficultway,withtheirdiseaseandtumorsoftenvisibletothepublic.Ihavebeeninvolvedinresearchforyearsaspartofscientists'decades-longendeavortobringforwardmeaningfuladvancesforpatientsdiagnosedwiththispotentiallyaggressivedisease.Untilrecently,suchadvanceswerehardtocomebyandmypatientsandIstruggledwiththelimitedtreatmentoptionsavailable.Butwhilethereisasignificantneedfornewtreatmentoptions,thegoodnewsisthattherehavebeensomeimprovementsinsurvivalratesovertheyearsandweareseeinganewandencouragingfutureahead.Wehavebeguntoleverageourunderstandingofbiologytodevelopmoreprecisetherapies.AtMSD,wearefocusedonimmuno-oncologyresearch,whichstudiestheroleoftheimmunesystemindetectingandfightingcancer.Wearestudyingthepotentialofthisapproach,whichaimstoharnessandrestorethebodysabilitytodetectandfightcancercells,inanumberofcancers,includingheadandneckcancer.Immuno-oncologyhasalreadysignificantlychangedthewaycertaincancersaretreated,includingmelanomaandlungcancer,aswellasinthetreatmentofheadandneckcancer.Changeiscomingtotheheadandneckcancerlandscape–anditisthrillingtobeapartofit.TobeabletoseehowourresearchandeffortsatMSDarehavingadirectimpactonhowphysiciansapproachthetreatmentoftheirpatientsandwhatpatientsmayexpectfromtheirtreatmentiswhatmotivatesustoworkharder.

  Historically,oncologypracticeandclinicaltrialdesignprimarilyfocusedonwherethetumorfirstemerged,suchascolonorrectum,lung,breast,andendometrium.Thisapproachfollowsthelogicofthescalpel:pinpointingthelocationofthetumorfirstenabledsurgicalplans.Morerecently,therehavebeensignificantadvancesinourunderstandingoftheroleofcancerbiomarkersinmolecularandcellularmechanismsthatcandrivetumorgrowth.Biomarkersarebiologicalmolecules(typicallycomprisedofDNA,RNAorprotein)foundintissuesorbloodthatcanserveasasigntobetterunderstandaconditionordisease.Sometimes,thesamebiomarkerisfoundacrossmanydifferenttypesofcancer,regardlessofwherethetumorfirstdeveloped.Withinaspecifictumorlocation,thesebiomarkerscansometimesdifferentiatewhetherthetumorislikelytorespondtoagiventreatment.Assuch,thesebiomarkershavebeenusedtohelpinformclinicalresearch,acceleratingtheprocessofgettingtargetedmedicinestopatientswhereseparatetrialswouldtakeyearstoconduct.Importantly,insomecases,thesefeaturescanbeassessedusinglaboratoryteststhathavelongbeenavailable.Whereatestiseithernotavailable,orforresearchuseonly,thetestmanufacturerpartnerswiththedrugmanufacturertoadvancetogetherintoregulatoryapprovalbygovernmentagencies(suchastheFDA)acompaniondiagnosticassaytoensuresafeandeffectiveuseofthedruginpatientslikelytorespond.Thegoalistouseadeeperunderstandingofthetumorbiologyandassociatedbiomarkerstotackletumorresearchmoreprecisely;goingbeyondsimplywhereatumorarose.Instead,wearelearninghowtoattackacancerbasedonitsbiologyatthecellularlevel.AtMSD,effortsareunderwaytobetterunderstandmicrosatelliteinstability(MSI)andmismatchrepairdeficiency(dMMR).Thesebiomarkersarepresentacrosstumortypes,regardlessoftheoriginallocationofthecancer.ThepresenceofhighlevelsofMSI(MSI-H)ordMMRsignifiesanunderlyingprobleminacell'sabilitytofixerrorsthatoccurwhenDNAreplicates.TumorcellsdeterminedtohaveMSI-HordMMRharborhundredstothousandsofmutations.Theultimateproofofoureffortswillmanifestasanewgenerationofcancermedicines:thosethatfollowthelogicofbiology,notthelogicofthescalpel.Jameslikeslogicpuzzles.Andwordproblems.Luckily,hegetstoapplytheseinterestsinhisworkeveryday.Jamesisacomputationalchemist–heworkswithMSD’schemistryteams,applyingpredictivemodellingtoidentifywaystodesigndrugsandanalyzedatatohelpourscientistsprioritizethenextcompoundstomakeandtest.Althoughthesearecomplexproblemsandcomplexquestionsthatwe’retryingtosolve,wetakelogicalsteps,explainsJames.Foreveryquestion,there’sreallyananswer,yousometimesjusthavetospendalittlebitmoretimethinkingaboutit,andtakeastepbackandlookatwhat’sactuallyinfrontofyou.Bettermolecules,fasterInourgroup’sroleindrugdiscovery,wehavethismantraof‘bettermolecules,faster,saysJames.Ifachemisthas100compoundsthatshe’sthinkingaboutmaking,computationally,wecanhelpprioritizewhichonestostartwithbasedonrationaldrugdesign.Jamesenjoysbeingpartofateamworkingtoachieveasingulargoal:tocreatemedicinesthatwillhelpthepeoplewhoneedthem.And,hebelievesthatcollaborationisveryimportantforresearchanddevelopment:Youcan'tdoaprojectonyourown;youneedotherstoassistandhelp,notjustbycontributingintheirindividualrole,butalsowiththeirthinking.Jamesandhiscolleagueshavealotofexperiencewithperseveranceanddetermination,too.Ourteamsofscientistsdesign,developandscreenthousandsofcompoundsandantibodiestoultimatelyadvanceonlyafewofthemostpromisingleadcandidatesintoclinicaltesting.Moleculardesignanddevelopmentisaniterativeprocess.Youhavetostickwithit.It'scontinuouslymakingmodificationsandadaptingandevolving,eventuallygettingdowntheroadorthepipelinetomakeadrug…that'swhat'sexcitingaboutit.It’sallaboutthepatientsEveryday,IcometoworkknowingthatI’mworkingtomakeadrug.And,Idon'tknowiftodayI’mgoingtoopenupanemailwithresultssaying,‘we'veaccomplishedthisor‘weneedtochangethat.’Butregardlessofwhatthoseresultsare,it'sgoingtobeprogresstogettothatendpoint.”“MyuncleIvanwasaseverediabetespatient—heneededinjectionsthreetimesaday.Hewaswithoutinsulinformorethanamonth.EvenIwasnotaware,”Pablorecounts.“Whenhefinallyreceivedinsulin,hewasinbadcondition.Severalweekslater,hishealthdeclined,hehadrenalfailure,andhedied.”ThedroneteamrecentlyacknowledgedPablo’scontributions,andhispersonalloss,bygivingtheprojectanewnickname.Oncecalled“MajorTom”aftertheDavidBowiesong,it’snow“ProjectIvan.”“Idon’thavewordsenoughtoshowmygratitude,”Pablosays.“Thisisaboutsavinglives.”

  Ourcompanyiscommittedtodiscoveringsmart,sustainablewaystoexpandaccesstohealthcare,especiallyinareaswithlimitedinfrastructureandresources.Giventhesignificanceofthischallenge,itisonlybyworkinginpartnershipwithothers—governments,donors,patientorganizations,healthcareprofessionals,NGOs,academicinstitutions,multilateralorganizationsandtheprivatesector—thatwecanwemakethestrongestcontribution.TheMSDFellowshipforGlobalHealthisbuiltonthenotionofpartneringtostrengthenthecapacityandreachofnonprofitorganizationswhich,inturn,willultimatelysolvesomeoftheworld’sgreatesthealthcarechallenges.Toexpressourappreciation,MSDbegan#DearCancerHeroes–asocialmediacampaigntorecognizetheirfortitudeandcontributionstothefield.It’sasmallgesturetoshowourgratitude.Wewanttoletclinicaltrialparticipantsknowtheyarenotaloneandthereisawholecommunityofpeoplecheeringthemon.Anyonecanjointhemovementbywritingamessagetocancerclinicaltrialparticipantsonastickynoteandsharingitonsocialmediausing#DearCancerHeroes.Cancerresearchhascomealongwayandstillhasalongwaytogo.However,wewouldn’thavegottentowherewearetodaywithouttheseheroes.Dr.Chenghasbeentreatingheadandneckcancerpatientsformanyyears.Thisishispersonalperspective.Ihavetreatedpatientswithheadandneckcancersformanyyears,soIhaveseen,upclose,thedifficultexperienceoflivingwithheadandneckcancer.Cancerisatryingsituationforallpatientsandtheirlovedones,butheadandneckpatientsfacecancerinauniqueanddifficultway,withtheirdiseaseandtumorsoftenvisibletothepublic.Ihavebeeninvolvedinresearchforyearsaspartofscientists'decades-longendeavortobringforwardmeaningfuladvancesforpatientsdiagnosedwiththispotentiallyaggressivedisease.Untilrecently,suchadvanceswerehardtocomebyandmypatientsandIstruggledwiththelimitedtreatmentoptionsavailable.Butwhilethereisasignificantneedfornewtreatmentoptions,thegoodnewsisthattherehavebeensomeimprovementsinsurvivalratesovertheyearsandweareseeinganewandencouragingfutureahead.Wehavebeguntoleverageourunderstandingofbiologytodevelopmoreprecisetherapies.AtMSD,wearefocusedonimmuno-oncologyresearch,whichstudiestheroleoftheimmunesystemindetectingandfightingcancer.Wearestudyingthepotentialofthisapproach,whichaimstoharnessandrestorethebodysabilitytodetectandfightcancercells,inanumberofcancers,includingheadandneckcancer.Immuno-oncologyhasalreadysignificantlychangedthewaycertaincancersaretreated,includingmelanomaandlungcancer,aswellasinthetreatmentofheadandneckcancer.Changeiscomingtotheheadandneckcancerlandscape–anditisthrillingtobeapartofit.TobeabletoseehowourresearchandeffortsatMSDarehavingadirectimpactonhowphysiciansapproachthetreatmentoftheirpatientsandwhatpatientsmayexpectfromtheirtreatmentiswhatmotivatesustoworkharder.

  Chemistryhasbeencentraltoourbusinessofsinceourearliestdaysasacompany.Historically,ourdrugdiscoveryprocessprimarilycenteredaroundsmallmolecules.Then,thebirthofbiotechnologyinthelate1970s/early1980saddedbiologics,orengineeredproteins,tothemix.Today,newmodalitiesareemergingthatshowastrongpotentialtotargetcomplexdiseasesthathavenotyetbeenreachablewitheithersmallmoleculesorbiologics.RobGarbaccioisleadingatalentedteamofchemistswhoarehelpingguideMSD’sentryintothisexcitingnewfieldofmedicine.IntroducinganddiscoveringnewwaysforwardRobistheassociatevicepresident,ChemistryCapabilitiesforAcceleratingTherapeutics(CCAT),adiscoverychemistryteamthatislookingathowtogobeyondthetraditionalmethodsofdiscoveringanddevelopingmedicines."Therearecertaindiseasetargetsthatarereallyhardto'reach'andimpactusingtraditionalmethods,"henotes."SopartofthegroupIoverseetriestofigureouthowwecanemploynewermodalities,suchaspeptides,bioconjugates,andoligonucleotides,toaddressthechallengingtargetsthatareincreasinglyemergingfrombiologicalresearch."Rob'sgroupisnotfocusedonanyspecifictherapeuticarea--theyareseekingnewwaystoaddressthemostdifficultdiseasetargets."Inoncology,infectiousdiseases,andneuroscience,forexample,we’relookingforthosetargetsthatourcolleaguessay,'Ifonlywecouldmodulatethistarget,webelievewemightbeabletopotentiallyinterruptthediseaseprocessandhelppatients,'"henotes.Using‘creativechemistry’totreatdiseaseIt'scomplexwork,tobesure,butthat'swhatmakesitsointriguingandinspiringforRobandhisteam."ThethingthatIlikethemostaboutmyworkisthebeliefthattheremaybeapathforwardforthetreatmentofeachandeveryoneofthesediseases.Wejustcan'tseeityetbecausethebiologyissocomplex,"saysRob."Asresearcherscontinuetoimproveourunderstandingofdiseasebiology,Ibelievethatcombiningthatknowledgewithcreativechemistrywillhelpleadusdownnewroadstotreatingdiseaseandhelpingpatients."Robjoinedthecompanyaftercompletinggraduateschoolandapostdoctoralfellowshipfocusingonorganicchemistry."Icameherebecausescienceandinnovationdrivethiscompany.I'mpassionateaboutourmissiontosaveandimprovelives,andIbelievethatmybestdayatwork,thedaymyteammakesapotentiallylife-changingdiscovery,isstillaheadofme,andit'sthereasonthatIstay."InventingforlifeAtMSD,wesayweare.AndRobdefinitelyseeshimselfasaninventor."Chemistshavethisuniqueabilitytocombineatomsandbondsbetweenatomsinauniqueway.Everydaychemistsareinventinghundredsofmoleculesthathaveneverexistedbefore.So,yes,weareinventing,"hesays."Weareinventingtosolveproblems."“MyuncleIvanwasaseverediabetespatient—heneededinjectionsthreetimesaday.Hewaswithoutinsulinformorethanamonth.EvenIwasnotaware,”Pablorecounts.“Whenhefinallyreceivedinsulin,hewasinbadcondition.Severalweekslater,hishealthdeclined,hehadrenalfailure,andhedied.”ThedroneteamrecentlyacknowledgedPablo’scontributions,andhispersonalloss,bygivingtheprojectanewnickname.Oncecalled“MajorTom”aftertheDavidBowiesong,it’snow“ProjectIvan.”“Idon’thavewordsenoughtoshowmygratitude,”Pablosays.“Thisisaboutsavinglives.”Chemistryhasbeencentraltoourbusinessofsinceourearliestdaysasacompany.Historically,ourdrugdiscoveryprocessprimarilycenteredaroundsmallmolecules.Then,thebirthofbiotechnologyinthelate1970s/early1980saddedbiologics,orengineeredproteins,tothemix.Today,newmodalitiesareemergingthatshowastrongpotentialtotargetcomplexdiseasesthathavenotyetbeenreachablewitheithersmallmoleculesorbiologics.RobGarbaccioisleadingatalentedteamofchemistswhoarehelpingguideMSD’sentryintothisexcitingnewfieldofmedicine.IntroducinganddiscoveringnewwaysforwardRobistheassociatevicepresident,ChemistryCapabilitiesforAcceleratingTherapeutics(CCAT),adiscoverychemistryteamthatislookingathowtogobeyondthetraditionalmethodsofdiscoveringanddevelopingmedicines."Therearecertaindiseasetargetsthatarereallyhardto'reach'andimpactusingtraditionalmethods,"henotes."SopartofthegroupIoverseetriestofigureouthowwecanemploynewermodalities,suchaspeptides,bioconjugates,andoligonucleotides,toaddressthechallengingtargetsthatareincreasinglyemergingfrombiologicalresearch."Rob'sgroupisnotfocusedonanyspecifictherapeuticarea--theyareseekingnewwaystoaddressthemostdifficultdiseasetargets."Inoncology,infectiousdiseases,andneuroscience,forexample,we’relookingforthosetargetsthatourcolleaguessay,'Ifonlywecouldmodulatethistarget,webelievewemightbeabletopotentiallyinterruptthediseaseprocessandhelppatients,'"henotes.Using‘creativechemistry’totreatdiseaseIt'scomplexwork,tobesure,butthat'swhatmakesitsointriguingandinspiringforRobandhisteam."ThethingthatIlikethemostaboutmyworkisthebeliefthattheremaybeapathforwardforthetreatmentofeachandeveryoneofthesediseases.Wejustcan'tseeityetbecausethebiologyissocomplex,"saysRob."Asresearcherscontinuetoimproveourunderstandingofdiseasebiology,Ibelievethatcombiningthatknowledgewithcreativechemistrywillhelpleadusdownnewroadstotreatingdiseaseandhelpingpatients."Robjoinedthecompanyaftercompletinggraduateschoolandapostdoctoralfellowshipfocusingonorganicchemistry."Icameherebecausescienceandinnovationdrivethiscompany.I'mpassionateaboutourmissiontosaveandimprovelives,andIbelievethatmybestdayatwork,thedaymyteammakesapotentiallylife-changingdiscovery,isstillaheadofme,andit'sthereasonthatIstay."InventingforlifeAtMSD,wesayweare.AndRobdefinitelyseeshimselfasaninventor."Chemistshavethisuniqueabilitytocombineatomsandbondsbetweenatomsinauniqueway.Everydaychemistsareinventinghundredsofmoleculesthathaveneverexistedbefore.So,yes,weareinventing,"hesays."Weareinventingtosolveproblems."

  Dr.Chenghasbeentreatingheadandneckcancerpatientsformanyyears.Thisishispersonalperspective.Ihavetreatedpatientswithheadandneckcancersformanyyears,soIhaveseen,upclose,thedifficultexperienceoflivingwithheadandneckcancer.Cancerisatryingsituationforallpatientsandtheirlovedones,butheadandneckpatientsfacecancerinauniqueanddifficultway,withtheirdiseaseandtumorsoftenvisibletothepublic.Ihavebeeninvolvedinresearchforyearsaspartofscientists'decades-longendeavortobringforwardmeaningfuladvancesforpatientsdiagnosedwiththispotentiallyaggressivedisease.Untilrecently,suchadvanceswerehardtocomebyandmypatientsandIstruggledwiththelimitedtreatmentoptionsavailable.Butwhilethereisasignificantneedfornewtreatmentoptions,thegoodnewsisthattherehavebeensomeimprovementsinsurvivalratesovertheyearsandweareseeinganewandencouragingfutureahead.Wehavebeguntoleverageourunderstandingofbiologytodevelopmoreprecisetherapies.AtMSD,wearefocusedonimmuno-oncologyresearch,whichstudiestheroleoftheimmunesystemindetectingandfightingcancer.Wearestudyingthepotentialofthisapproach,whichaimstoharnessandrestorethebodysabilitytodetectandfightcancercells,inanumberofcancers,includingheadandneckcancer.Immuno-oncologyhasalreadysignificantlychangedthewaycertaincancersaretreated,includingmelanomaandlungcancer,aswellasinthetreatmentofheadandneckcancer.Changeiscomingtotheheadandneckcancerlandscape–anditisthrillingtobeapartofit.TobeabletoseehowourresearchandeffortsatMSDarehavingadirectimpactonhowphysiciansapproachthetreatmentoftheirpatientsandwhatpatientsmayexpectfromtheirtreatmentiswhatmotivatesustoworkharder.Chemistryhasbeencentraltoourbusinessofsinceourearliestdaysasacompany.Historically,ourdrugdiscoveryprocessprimarilycenteredaroundsmallmolecules.Then,thebirthofbiotechnologyinthelate1970s/early1980saddedbiologics,orengineeredproteins,tothemix.Today,newmodalitiesareemergingthatshowastrongpotentialtotargetcomplexdiseasesthathavenotyetbeenreachablewitheithersmallmoleculesorbiologics.RobGarbaccioisleadingatalentedteamofchemistswhoarehelpingguideMSD’sentryintothisexcitingnewfieldofmedicine.IntroducinganddiscoveringnewwaysforwardRobistheassociatevicepresident,ChemistryCapabilitiesforAcceleratingTherapeutics(CCAT),adiscoverychemistryteamthatislookingathowtogobeyondthetraditionalmethodsofdiscoveringanddevelopingmedicines."Therearecertaindiseasetargetsthatarereallyhardto'reach'andimpactusingtraditionalmethods,"henotes."SopartofthegroupIoverseetriestofigureouthowwecanemploynewermodalities,suchaspeptides,bioconjugates,andoligonucleotides,toaddressthechallengingtargetsthatareincreasinglyemergingfrombiologicalresearch."Rob'sgroupisnotfocusedonanyspecifictherapeuticarea--theyareseekingnewwaystoaddressthemostdifficultdiseasetargets."Inoncology,infectiousdiseases,andneuroscience,forexample,we’relookingforthosetargetsthatourcolleaguessay,'Ifonlywecouldmodulatethistarget,webelievewemightbeabletopotentiallyinterruptthediseaseprocessandhelppatients,'"henotes.Using‘creativechemistry’totreatdiseaseIt'scomplexwork,tobesure,butthat'swhatmakesitsointriguingandinspiringforRobandhisteam."ThethingthatIlikethemostaboutmyworkisthebeliefthattheremaybeapathforwardforthetreatmentofeachandeveryoneofthesediseases.Wejustcan'tseeityetbecausethebiologyissocomplex,"saysRob."Asresearcherscontinuetoimproveourunderstandingofdiseasebiology,Ibelievethatcombiningthatknowledgewithcreativechemistrywillhelpleadusdownnewroadstotreatingdiseaseandhelpingpatients."Robjoinedthecompanyaftercompletinggraduateschoolandapostdoctoralfellowshipfocusingonorganicchemistry."Icameherebecausescienceandinnovationdrivethiscompany.I'mpassionateaboutourmissiontosaveandimprovelives,andIbelievethatmybestdayatwork,thedaymyteammakesapotentiallylife-changingdiscovery,isstillaheadofme,andit'sthereasonthatIstay."InventingforlifeAtMSD,wesayweare.AndRobdefinitelyseeshimselfasaninventor."Chemistshavethisuniqueabilitytocombineatomsandbondsbetweenatomsinauniqueway.Everydaychemistsareinventinghundredsofmoleculesthathaveneverexistedbefore.So,yes,weareinventing,"hesays."Weareinventingtosolveproblems."“MyuncleIvanwasaseverediabetespatient—heneededinjectionsthreetimesaday.Hewaswithoutinsulinformorethanamonth.EvenIwasnotaware,”Pablorecounts.“Whenhefinallyreceivedinsulin,hewasinbadcondition.Severalweekslater,hishealthdeclined,hehadrenalfailure,andhedied.”ThedroneteamrecentlyacknowledgedPablo’scontributions,andhispersonalloss,bygivingtheprojectanewnickname.Oncecalled“MajorTom”aftertheDavidBowiesong,it’snow“ProjectIvan.”“Idon’thavewordsenoughtoshowmygratitude,”Pablosays.“Thisisaboutsavinglives.”

  Chemistryhasbeencentraltoourbusinessofsinceourearliestdaysasacompany.Historically,ourdrugdiscoveryprocessprimarilycenteredaroundsmallmolecules.Then,thebirthofbiotechnologyinthelate1970s/early1980saddedbiologics,orengineeredproteins,tothemix.Today,newmodalitiesareemergingthatshowastrongpotentialtotargetcomplexdiseasesthathavenotyetbeenreachablewitheithersmallmoleculesorbiologics.RobGarbaccioisleadingatalentedteamofchemistswhoarehelpingguideMSD’sentryintothisexcitingnewfieldofmedicine.IntroducinganddiscoveringnewwaysforwardRobistheassociatevicepresident,ChemistryCapabilitiesforAcceleratingTherapeutics(CCAT),adiscoverychemistryteamthatislookingathowtogobeyondthetraditionalmethodsofdiscoveringanddevelopingmedicines."Therearecertaindiseasetargetsthatarereallyhardto'reach'andimpactusingtraditionalmethods,"henotes."SopartofthegroupIoverseetriestofigureouthowwecanemploynewermodalities,suchaspeptides,bioconjugates,andoligonucleotides,toaddressthechallengingtargetsthatareincreasinglyemergingfrombiologicalresearch."Rob'sgroupisnotfocusedonanyspecifictherapeuticarea--theyareseekingnewwaystoaddressthemostdifficultdiseasetargets."Inoncology,infectiousdiseases,andneuroscience,forexample,we’relookingforthosetargetsthatourcolleaguessay,'Ifonlywecouldmodulatethistarget,webelievewemightbeabletopotentiallyinterruptthediseaseprocessandhelppatients,'"henotes.Using‘creativechemistry’totreatdiseaseIt'scomplexwork,tobesure,butthat'swhatmakesitsointriguingandinspiringforRobandhisteam."ThethingthatIlikethemostaboutmyworkisthebeliefthattheremaybeapathforwardforthetreatmentofeachandeveryoneofthesediseases.Wejustcan'tseeityetbecausethebiologyissocomplex,"saysRob."Asresearcherscontinuetoimproveourunderstandingofdiseasebiology,Ibelievethatcombiningthatknowledgewithcreativechemistrywillhelpleadusdownnewroadstotreatingdiseaseandhelpingpatients."Robjoinedthecompanyaftercompletinggraduateschoolandapostdoctoralfellowshipfocusingonorganicchemistry."Icameherebecausescienceandinnovationdrivethiscompany.I'mpassionateaboutourmissiontosaveandimprovelives,andIbelievethatmybestdayatwork,thedaymyteammakesapotentiallylife-changingdiscovery,isstillaheadofme,andit'sthereasonthatIstay."InventingforlifeAtMSD,wesayweare.AndRobdefinitelyseeshimselfasaninventor."Chemistshavethisuniqueabilitytocombineatomsandbondsbetweenatomsinauniqueway.Everydaychemistsareinventinghundredsofmoleculesthathaveneverexistedbefore.So,yes,weareinventing,"hesays."Weareinventingtosolveproblems."Ourcompanyiscommittedtodiscoveringsmart,sustainablewaystoexpandaccesstohealthcare,especiallyinareaswithlimitedinfrastructureandresources.Giventhesignificanceofthischallenge,itisonlybyworkinginpartnershipwithothers—governments,donors,patientorganizations,healthcareprofessionals,NGOs,academicinstitutions,multilateralorganizationsandtheprivatesector—thatwecanwemakethestrongestcontribution.TheMSDFellowshipforGlobalHealthisbuiltonthenotionofpartneringtostrengthenthecapacityandreachofnonprofitorganizationswhich,inturn,willultimatelysolvesomeoftheworld’sgreatesthealthcarechallenges.In1962hercollaborators,JamesWatson,FrancisCrickandMauriceWilkinswereawardedtheNobelPrizefortheir“discoveriesconcerningthemolecularstructureofnucleicacidsanditssignificanceforinformationtransferinlivingmaterial.”Franklin’suntimelydeathdeniedhertheacclaimofthisprestigiousscientificaward(theNobelCommitteedoesnotawardtheprizeposthumously),butherroleinthisfundamentaldiscoveryhasbeenwelldocumentedandisnowwidelyrecognized.Franklin’sstoryofalifecutshortbyovariancancerremainsalltoocommon.Eventoday,advancedovariancancerremainsoneofthemostdifficultcancerstotreat.Butthereremainsareasonforoptimism.Thepaceofchangeincancertreatmenthasincreaseddramaticallyinrecentyears.Advancesinresearch–manyofwhichmaybetracedbacktoFranklin’swork–havegivenusadeeperunderstandingofhowtotargetthedisease,pavingthewayfornewdevelopments.Specifictoovariancancer,recentclinicalresearchhasshownpromiseforwomenwithadvancedstagesofthedisease.AtMSD,wearefocusedontranslatingbreakthroughscienceintooncologytherapeuticsthathavethegreatestpotentialforimprovinglong-termdiseasecontrolandsurvivalforpatients,includingthosewithovariancancer.Werecognizethatnotwopatientsorcancersarethesameandmultipleapproaches–therapeuticregimensandmechanismsofaction–willbeneededtooutpacethisdisease.That’swhywehaveworkedrigorouslytoexpandanddiversifyourowninternalresearchprograms.Thereisstillworktobedone,butwebelievestronglyinourpotentialtotransformthewayallcancersaretreated.AndweareconstantlyinspiredtoworkharderbystorieslikeRosalindFranklin’s.

责任编辑:www.22sbc.com_www.22sbc.com-【让你轻松】社友网:未经授权不得转载
关键词 >>

继续阅读

热新闻

热话题

热门推荐

关于我们 联系我们 版权声明 网站地图
百站百胜: “女儿11岁,怀孕5个月”:我拼命保护的孩子,却毁在性… 曝梅西和阿根廷队一直存在隔阂足协拿他当摇钱树 直击|飞猪回应北京消协报告:不会利用大数据杀熟 再次落空暗物质新实验未发现轴子证据 从赛车到民用版曝DaciaDusterEV谍照 全球投资者青睐马德里豪宅 想要12艘航母?美海军玩了招“以退为进” 恺英网络实控人\"失联\":自称不懂游戏曾收购贪玩蓝… “火烧赤壁”准备一年有余航拍镜头耗18万资金 深圳主帅:会教导球员控制情绪下半场打出了精神 联储官员回应降息疑云:保持耐心近期不可能经济衰退 英超第一战将谈未来:看到球队的野心才会留队 大新金融18年股东应占溢利减少64.6%至19.15亿… 外资评级机构加速入华:这轮想要更多中资机构难抗衡 产后妈妈要适当下床活动 大西雅圖地區賞花地圖,櫻花、鬱金香、山茶、水仙去這些地… 拐点已至?招行等前五大私人银行AUM增速悉数放缓 “补贴时代”进入尾声:新能源车市场面临大洗牌 蒙牛凶猛不再:曾经的乳业之王为何被伊利甩在身后? 贤能集团取消厦门商住空间项目由南安项目取代 谢娜称已让赵丽颖看《妻子》:希望她一起来旅行 香港特区区旗设计者辞世特首悼念 起底“仅剩半条命”的家盒子 永利澳门升幅扩至逾6%惟首季澳门赌收跌0.5% 《都挺好》家庭,爱和被爱与面对和成长 金一南:特朗普最近这个决定会让世界大乱 工商银行资产减值损失升26.5%至1615.94亿元 广发证券去年盈利按年减少近50%不派息 直击|微软洪小文:对用户来说,方便和隐私互相冲突 苹果变\"软\"了这届网友的态度却很“硬”! 加快大数据立法遏制隐私信息“裸奔” 浓浓年代感!郭富城老粉问《创2》在哪个电视台播 国外土豪们喜欢在朋友圈晒什么酒? 3月29日金投赏启动会“用创新迎来增长” 冰壶世锦赛巴德鑫替补难救主中国负日本两连败 百日民調盧秀燕:虛心以待好好努力 2019西安国际摄影月开幕18岁青年摄影师引关注 14亿额度10分钟售罄浙江两地方债遭个人投资者疯抢 从传统零售变身科技公司,沃尔玛如何抢占AI风口? 美国华人清明扫墓:祭奠方式不同缅怀的心意一致 苹果在流媒体电视行业五大领域各有哪些对手? 京津冀周边“2+26”城市PM2.5排名:安阳浓度最高 来电与街电专利纠纷:来电一项专利一审被判无效 崇礼区冰雪博物馆全球征集活动启事时间长期有效 调查-中国杯国足垫底原因在哪?究竟要怎样的教练? 女足队长盛赞凤凰球衣:是独特标志穿上能提升信心 收评:港股恒指涨0.21%医药股、博彩股走高 小米9累计备货突破150万雷军不用去工厂拧螺丝啦 沈阳发生纵火爆炸袭警案3人受伤嫌犯当场身亡 均衡的代步小车试驾江铃集团新能源——易至EV3 曾经火爆一时如今亏损5亿!美图手机彻底凉了 克鲁小丑因纪录片再受关注原声碟入围公告牌前十 3分22中2!火箭三兄弟狂打铁这么惨只赢过一场 《雷神3》导演参演新片《自由人》对戏“死侍” 大选变海选乌克兰要诞生第一个“戏精”总统了? 调查:英国金融业前景展望降至2008年以来最低 历史上的无盈利牛市:无盈利,也疯狂? 美国母亲呼吁女生不穿紧身裤:给男生太多性暗示了 23岁牺牲消防员杨瑞伦家属:我们全家以他为傲 网红奶茶店排班软件走红:资本争抢万亿级大生意 “证”合我意4月1日起出入境证件“全国通办” 小米扛着一场战役:可能是雷军最好也是最后一次机会 博鳌嘉宾共议“一带一路”:鼓励各国私人资本参与 乍暖还寒学江疏影唐嫣穿时髦廓形西装抵御早晚温差 瑞风M3/R3新增车型上市售价7.48-9.58万 众泰i-across设计图发布上海车展首发 韦世豪谈铲人:太想赢不是故意的伤病难免很正常 研究:黄金与黄金股谁是鸡谁是蛋? 本赛季各点最准的人:书豪上榜KD称霸两侧底线 响应增值税下调政策五菱宝骏最高优惠3.8万 在这个领域台湾还要追赶大陆很久 太惨!阿森纳要卖人省钱厄齐尔+姆希塔良全走 芝加哥联储主席:美经济面临的下行风险大于上行风险 谷歌脸书亚马逊日子难过IMF呼吁对跨国大型科企加税 嘉年华国际今早复牌现急涨逾两成录得亏损30亿元 花旗:中国太保目标价升至38元维持买入评级 福建只抵抗两节!一波18-0背后是多少年的积淀 健身的男人都很帅,请珍惜身边健身的男人 下周四马斯克与SEC律师将在4月4日进行口头辩论 3岁男娃误吞7颗“巴克球”胃肠12处穿孔 积极响应国家政策福特下调中国大陆进口车售价 “小”数据意外抢走恐怖数据风头今日还有一件大事 A股史上第六次牛市正在酝酿股改后最强牛市袭来? 谈资|网红和小作坊纷纷卖假包,你买的奢侈品还能是真… 俄军战舰在日本海举行反潜训练向假想敌发射鱼雷 Needham:苹果流媒体视频服务是Netflix的“… 热身赛-U19男足3-2再胜缅甸四战两胜两负位居第三 是什么支撑你走过人生最艰难的时刻? OLED产业5年后将被中国超越韩国官员着急了 麦当劳将不再游说反对提高最低工资 百亿团贷网案犯自首此前投资人报案超15.47万宗 金正男被杀案越南女嫌犯罪名减轻判3年4个月监禁 中国成美国第一假想敌?美国务卿“要钱”制衡中俄 “铁饭碗”不好端也不好丢这5类人不得辞职 外交部:这份“机密文件”你从哪得来的? 医学研究生160斤肥壮身材照样吸粉百万 一波又起!葛振踹人被马宁红牌罚下场上10打10 放棄十億流量頻道鄧紫棋另起爐灶 高校教师称项目申请书遭泄密剽窃湖南大学回应学生抄袭 管理资金超300亿的谢治宇:年初的上涨只是导火索 周三黄金期货下跌0.4%创近一周来新低 华晨宇同学曝其昔日恋情分手后躲车里偷看旧爱 上周东西部最佳球员:哈登与特雷-杨当选 易建联获最佳防守队员奖杯:比我家水果盘还重 如何看待美债收益率曲线倒挂?这是高盛的观点 当男人愿意给你这三样东西时,说明他爱你到骨子里了! 早田希娜奥运资格形势严峻称国际赛拼死多赢中国 响应国家降税名爵部分车型最高优惠2.9万元 國安基金條例修正案明審查財部傾向維持原條文 5亿票据纠纷银行诉讼案:员工收150万帮企业融资5亿 美国1月份贸易逆差收窄进口中国商品大幅下降 彰化表揚模範兒童營造安全優質成長環境 李颖:工业互联网既不姓工也不姓互是新生命的诞生 助力“一带一路”倡议天荣与国际摩联携手共进 首份国有大行年报来了邮储银行营收2612亿元 美银美林:海尔电器目标价升至25元维持买入评级 瑞信:中国重汽目标价升至9.3元维持跑输大市评级 花旗:复星国际目标价升至17元维持买入评级 “缩表”之变对海外中资股影响如何? 运动防心梗!长期运动可以刺激血管分泌外泌体 科比新书登畅销书排行榜第一!魔幻题材谁不爱 加快\"南融\"步伐湖南永州争当承接产业转移\"领头… 孙宏斌:融创不想做第一很多年现阶段效益第一 路威复出快船拒绝连败勒夫缺阵骑士连失五城 斗鱼年收入破40亿计划年内启动赴美上市 凤凰卫视出售一点科技料有22.93亿港元收益 彰化推糞土變綠金 養豬場沼氣發電冠全台 日本民间智库担忧“改元十连休”或有损经济 挂着雷克萨斯标的埃尔法要来了那么问题来了,加价几十万… 美股盘前:衰退幽灵重现股指期货小幅下滑 Lyft宣布IPO定价为72美元周五登陆纳斯达克 A股放量大涨:两市成交额再破万亿近200股涨停 汽车坠下州立公园500英尺悬崖司机命丧当场 与奔驰EQA同平台宝马i2或将于2024年上市 大家乐集团:罗碧灵将由执行董事调任为非执行董事 许茹芸李心洁为梁咏琪庆生小黄花姐妹团感情依旧 中国外文出版发行事业局高岸明:“求同存异”应传播 “三桶油”业绩PK:中海油日赚1.44亿再度逆袭 销量数据引质疑押注线上销售的特斯拉能否赢未来? 马斯克的“复仇”:铁了心要“毁灭”泄密者 高盛:华润置地目标价升至41.1元给予买入评级 随着对全球经济增长的担忧加剧投资者纷纷买入债券 中概股周一多数上涨:微博涨逾7%趣头条跌逾8% 华少近照曝光又胖了,看到他的伙食我明白了原因! 比首胜还爽!泰达有个阿森纳!最强快刀也回来了 姜丹尼尔方谈解约纠纷:不会一一回应对方主张 【DC賞櫻聖地】在春天去做一場粉色的夢 武汉坠亡硕士导师王攀道歉支付抚慰金65万元人民币 3月北京二手房成交超1.6万套创近10个月新高 刘晓春:金融供给侧改革的重点是保证供给能力更有效 李宁公司8年来首次派息之后遭非凡中国减持套现 博鳌观点:5G将给金融科技带来跨跃式发展 土耳其动用外汇储备支撑里拉本月已消耗三分之一 疯狂的工业大麻:有公司一棵麻苗还没种股价却翻了天 吴欣鸿:美图急需解决的问题是用户重回高速增长轨道 华为P30系列评测:DxO第一的水平究竟如何 梅西直追贝利上古神纪录!只差50球下赛季就能破 2019春交会开幕孙红雷张翰新剧亮相贺国诞70周年 被邊緣化?柯文哲:差不多了 人到中年,这样做夫妻更好 山东应急厅督查:德州涉硝基化合物企业已两家停产 江苏盐城爆炸事故:政府承诺负责所有受损房屋修缮 从甲骨文收购动作来看一切都是为了重振云计算? 外媒:爱奇艺完成12亿美元可转换优先债券发行 宝宝树2018年营收7.6亿元调整后利润2.01亿元 GooglePlay商店下架“性向转变”治疗应用 羽生结弦吃止痛药战世锦赛:正因尊敬陈巍才更想赢 体验优续航短场地体试驾大众国产电动新车 26+9+5三分!金州的王回来了欠他的FMVP该还了 小摩:远洋集团降至中性评级目标价下调至3.2元 瑞信:中国财险降至中性评级目标价下调至9.5元 6岁近视率5.9%15岁近八成女生近视率明显高于男… 波音发布737Max软件补丁表示飞机将更为安全 鸿腾精密:GILLESPIEWilliamRalp… 美银美林:润地目标价升至37元重申买入评级 F1H2O沙特大奖赛前瞻天荣队战力满血志夺开门红 私募冠军崔军:超级大牛市已启动沪指有望冲击8000点 日本歌迷悼念张国荣离世16年1339只千羽鹤有寓意 周杰伦转发阿信求救文逗趣吐槽对方:怎么不早说 股汇双杀利率飙升土耳其连中三刀能挺过去吗 容祖儿出道20周年开唱拒绝变瘦原因曝光 沃神:在交易时,尼克斯就已告知波神被指控强奸 颐海国际走高超过半成破顶去年多赚99% 胡歌肖像权姓名权遭商家侵犯委托律师发声明维权 球迷热议国足垫底:恭喜闯进四强中国杯劳民伤财 马斯克:特斯拉的交付团队完成了“令人惊叹”的工作 FE电动方程式赛事再掀中国攻势新浪全方位助力 A妹将与维多利亚合作发新歌有望实现八周连冠 谷歌母公司给Lyft投资5亿美元17个月内价值翻倍 金融科技境外上市首现反向收购案网信普惠将上美股 北方矿业去年亏损4.8亿元不派息 响水爆炸事故现场搜救工作正式结束搜救出164人 曝魔术师本赛季曾错过巴特勒!他夏天想来LA? 2018年四大行开发贷余额突破3万亿同比增长12.7… 牛!利物浦天王史诗级1防2这霸气英超独一份|gif 44岁李玟自曝冻龄靠科技,网友:真是耿直girl 范丞丞自曝心酸日常:每天只睡两三个小时