中山大學(xué)循證醫(yī)學(xué)3TranslationalMedicine-ZSU-FS

TranslationalMedicine

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PersonalizedMedicine轉(zhuǎn)化醫(yī)學(xué)和個(gè)體化醫(yī)學(xué)楊學(xué)寧XueningYang,MD廣東省人民醫(yī)院GuangdongGeneralHospital廣東省肺癌研究所GuangdongLungCancerResearchInstitute《循證醫(yī)學(xué)》雜志JournalofEvidence-basedMedicine1h第1頁(yè)EBPModelsTraditionalpracticeModel(×)Model1:UsethehighestqualityinformationtoguideclinicaldecisionsModel2:Search,evaluate,andmakeavailablespecialtyspecificLevel1informationModel3:CreateoriginalresearchorsystematicreviewsModel4:Translationalresearch……2h第2頁(yè)BackgroundInthepast30years，NCI$200BillionsResults：1.56millionarticles80％onmice,fruitflyandroundworm。Nochangeoncancerrelatedmortalityrate3h第3頁(yè)Background4h第4頁(yè)BackgroundNewbiotechnologyGenomics(基因組),Proteomics(蛋白質(zhì)組)Bioinformatics(生物信息學(xué))Increasingcomplexityofclinicalresearch5h第5頁(yè)DefinitionTranslationalresearch,“transformsscientificdiscoveriesarisingfromthelaboratory,clinical,orpopulationstudiesintoclinicalapplications…”Include：benchtobedside(基礎(chǔ)研究到臨床應(yīng)用)bedsidetobench(臨床治療成果促進(jìn)基礎(chǔ)研究)Source:NationalCancerInstitute,NationalInstitutesofHealth6h第6頁(yè)Definition

ClinicLabPopulationT1T2T1:applyingbasicsciencefindingsfromlabresearchinclinicalstudiesofpatientsT2:applyingthefindingsofclinicalstudiestoalterhealthpracticesinthecommunityEBMTranaslationalMedicinePersonalizedMedicine7h第7頁(yè)Goals/PurposeT1:Theproductionofapromisingnewtreatment/methodthatcanbeusedclinicallyorcommercialized.T2:Ensurethatnewtreatmentsandresearchknowledgeactuallyreachthepatientsorpopulationsforwhomtheyareintendedandareimplementedcorrectly8h第8頁(yè)ResearchcontentT1:totest,inhumans,thenoveltherapeuticstrategiesdevelopedthroughexperimentation(exvivoorfrom-bench-to-bedside)

T2:totesthowcanefficientlyuseclinicalresultstooptimizehealthpracticesandimproveguidelinesandhealthpolicy(from-bedside-to-population)9h第9頁(yè)Settings/knowledgebackgroundT1:requiresmasteryofmolecularbiology,genetics,andotherbasicsciences;clinicalscientistsworkinginstronglaboratoriesandwithcutting-edgetechnology;asupportiveinfrastructurewithintheinstitution.T2:the“l(fā)aboratory”forT2researchisthecommunityandambulatorycaresettingsmasteryofthe“implementationscience”offieldingandevaluatinginterventionsinrealworldsettingsmasteryofthedisciplinessuchasclinicalepidemiologyandevidencesynthesis,communicationtheory,behavioralscience,publicpolicy,financing,organizationaltheory,informatics,andmixedmethods/qualitativeresearch.10h第10頁(yè)ChallengesT1:strugglesmorewithbiologicalandtechnologicalmysteries,trialrecruitment,andregulatoryconcernsT2:strugglesmorewithhumanbehaviorandorganizationalinertia,infrastructureandresourceconstraints,andthemessinessofprovingtheeffectivenessof“movingtargets”underconditionsthatinvestigatorscannotfullycontrol11h第11頁(yè)InvestigatorsT1:BasicscientistscooperatewithclinicaldoctorsT2:Population-basedinvestigatorsandepidemiologistsandhealthpolicymakers,etc...Moreeffectivecollaborationbetweenlabscientistsandclinicaldoctors12h第12頁(yè)TranslationalMedicineDisseminationoftheinnovationAdoptionoftheinnovationMaintainingtheinnovationRefiningandevolvingasbodyofknowledgeexpands13h第13頁(yè)TheTranslationContinuumBasicScientificDiscoveryEarlyTranslationLateTranslationDisseminationAdoptionPromisinggeneBasicepidemiologicalfindingPartnershipsInterventiondevelopmentPhaseIIItrialsRegulatoryapprovalPartnershipsHealthservicesresearchtosupportdisseminationandadoptionTocommunityprovidersTopatientsandpublicAdoptionofadvancebyproviders,patients,andpublicPaymentmechanismstoenableadoptionSource:NationalCancerInstitute14h第14頁(yè)TranslationalMedicineTranslatethesuccessingenomicmedicineintoclinicalapplicationsEvidence-basedmedicinedeveloprationaleandtheoryfordrugdesignandtherapeuticinterventionDeveloppersonalmedicineandpreventivemedicine15h第15頁(yè)TranslationalMedicineTranslationalResearch-hotspotGenomicandgenediagnosisandtreatment基因組研究及基因診斷治療PhaseItrialfordrugs藥品一期臨床試驗(yàn)GenomicPharmocologyandpersonalizedmedicine基因組藥理學(xué)與個(gè)體化醫(yī)學(xué)Biomarks生物標(biāo)識(shí)物Signaltransductingpathwayandclinicalapplications信號(hào)傳導(dǎo)通路研究及其臨床應(yīng)用Stemcell干細(xì)胞16h第16頁(yè)TranslationalMedicineTheheartoftranslationalresearchresidesinPhaseItrialswherenoveltreatmentsare：testedforfeasibilityandtoxicitypreparationforaPhaseIItrialinwhichtherapeuticeffectivenessistestedMarincola,FMTranslationalMedicine:Atwo-wayroad,JTM,202317h第17頁(yè)ClinicalResearchTrainingProgramComputerSkillsClinicalResearchMethodsBiostatistics:StatisticalApproachinClinicalResearchMeasurementsinClinicalResearchEthicsandRegulationsofClinicalResearchResearchDesignandDevelopmentCost-effectivenessAnalysisRegressionandANOVALogisticRegressionClinicalTrials18h第18頁(yè)TheprocessofTranslationChoosearesearchtopicrelatedtoyourclinicalpractice19h第19頁(yè)EarlystudyonnitricoxideSynthase20h第20頁(yè)UsesforaclonedgeneHomologycomparisonQuantitategeneexpressionChromosomalmappingDeterminetranscriptionalregulationPreparerecombinantproteinAntibodydevelopmentTissuelocalizationDeveloptransgenic/knockoutanimalsGenetransfer/genetherapystudiesIntellectualproperty/technologytransfer21h第21頁(yè)22h第22頁(yè)ExploreGeneandDiseases23h第23頁(yè)24h第24頁(yè)P(yáng)hysiopathologicalStudyBench:VasoprotectivePropertiesofNitricOxideInhibitsplateletaggregationInhibitsleukocytechemotaxisInhibitsVSMCproliferationInhibitsVSMCmigrationPromotesECgrowthInhibitsECapoptosisPotentvasodilator25h第25頁(yè)CellandAnimalAdenoviralVector(type5,E1-,E3-)腺病毒載體26h第26頁(yè)SmallAnimals27h第27頁(yè)BiggerAnimals28h第28頁(yè)AnimalExperiment2023年29h第29頁(yè)30h第30頁(yè)P(yáng)haseⅠClinicalTrialClinicalTrial:AdiNOSgenetherapytoblockAVfistulaneointimalhyperplasiainhemodialysispatients202331h第31頁(yè)CurrentStateofTranslationalMedicine17yearinnovationadoptioncurvefromdiscoveryintoacceptedstandardsofpracticeEvenifastandardisaccepted,patientshavea50:50chanceofreceivingappropriatecare,a5-10%probabilityofincurringapreventable,anticipatableadverseeventThemarketisbalkingathealthcareinflation,newdiagnosticsandtherapeuticswillfindincreasingresistanceforreimbursement32h第32頁(yè)P(yáng)ersonalizedMedicine

ClinicLabPopulationT1T2T1:applyingbasicsciencefindingsfromlabresearchinclinicalstudiesofpatientsT2:applyingthefindingsofclinicalstudiestoalterhealthpracticesinthecommunityEBMTranaslationalMedicinePersonalizedMedicine33h第33頁(yè)P(yáng)ersonalizedmedicinetheapplicationofgenomicandmoleculardatatobettertargetthedeliveryofhealthcare,facilitatethediscoveryandclinicaltestingofnewproducts,andhelpdetermineaperson'spredispositiontoaparticulardiseaseorconditionapatient'sprotein,geneormetaboliteprofilecouldbeusedtotailormedicalcaretothatindividual'sneeds34h第34頁(yè)ImatinibforGISTGIST

genesisKeyprocess：c-kitmutation---KITTKactivationPDGFRmutation86%

GIST

kitmutation，prognosisfactorImatinibOralsmallmoleculeTKIInhibitTKactivation抑制酪氨酸激酶活化Designforchronicmyeloidleukemia(CML)35h第35頁(yè)ImatinibforGIST36h第36頁(yè)ImatinibforGISTJoensuuH，etal.202337h第37頁(yè)P(yáng)retreatmentOnemonthoftherapyH&E(atdiagnosis)H&EKi67CD117JoensuuHetal.NEnglJMed.2023;344:1052-1056.TheFirstGISTPatient:HistologyImatinibforGIST38h第38頁(yè)ImatinibforGISTJoensuuH，etal.2023Theory：ImatinibcouldtargetGISTEasyDetectedtumormarker：CD117TissuefromthepatientResponseconfirmedbypathologyDynamicmonitoredbytumormarkerEthics：IRB39h第39頁(yè)Imatinib治療GIST2023.3：JoensuuH.firstcase2023.7：

phaseIIstudy(B2222)

2023autumn：phaseIIstudy(S0033,EORTC)2023.2：FDA40h第40頁(yè)41h第41頁(yè)ImatinibforGIST5-year