肿瘤分子靶向治疗的思考

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1、BATTLEPROGRAMBiomarker-basedApproachofTargetedTherapyforLungCancerElimination.WaunKiHongetalBiomarkerAnalysisinCoreBiopsy￫SelectAdequateTargetTherapy未来的方向加强癌症基因分型及药物基因学研究，寻找各种靶向治疗药物的适用或预测指标。Treatingtumorsaccordingtotheirmoleculardefectsandtheirupgradedordowngradedsignaltransductionpa

2、thways.ClinicalPredictorsofGefitiniborErlotinibEfficacyinNSCLCNeversmokerFemalegenderAdenocarcinomaBronchoalveolaradenocarcinomaAsianorigin肿瘤分子靶向治疗的思考中山大学肿瘤防治所管忠震分子靶向治疗研究的兴起上世纪70-80年代，癌症生物学研究迅速发展，从分子水平了解肿瘤发生、发展的机制。Scientificresearchhasincreasinglyidentifiedkeygeneticeventscriticaltos

3、peceficcancerdevelopment.TargetingTherapyAnewgenerationofsmallmoleculesorMABsthatrationalydesigndetoinhibitspecificsignaltransductionortranscriptionpathwaysthatarecriticalforcancercellgrowthandsurvival.EGFRBlockadeasCancertherapyTheEGFRautocrinepathwaysplaysanimportantroleinthedevelo

4、pmentandprogressionofhumanepithelialcancer.EGFRactivationtriggersacascadeofsignalsleadingtocellproliferation,productionofantiogenicfactorsandpromotionofinvasionandmetastasis.HighexpressionofEGFRiscommoninawidevarietyofhumancancersandisgenerallyassociatedwithadvanceddiseaseandpoorprog

5、nosis,andwithresistancetohormonetherapy,chemotherapy,orradiotherapy.EGFRBlockadeasCancerTherapy:J.mendelsohn’sHypothesis(Early1980s)TheblockadeofEGFRactivationmayinhibitcancrcellproliferation.CancercellsmaybeselectivelysensitivetoEGFRinhibitionascomparedtonormalcells.Selectiveanti-E

6、GFRagentsmaybedeveloped.靶向治疗研究已获得明显成果GleevecNorvatisCML,GISTGefitinibAstraZenicaNSCLCErlotinibGenetech,RocheNSCLCErbituxImClone,MerchCRC,H/NHerceptinGenetech,RocheBreastBevacezumabRocheCRC,lungSorafenibBayerRCCSunitinibPfeizerRCC,GIST许多新的分子靶向药物仍在开发研究中ZD6474(Vandetanib)AZlungGW786034(

7、Pazopanib)GSKRCCCA163048(lxabepilone)BMSBreastEGF10453(Lapatinib)GSKBreastEnzastaurinEil-lillyGBM,NHLDasatinib耐药CMLPF3512676Pfeizerlung靶向治疗药物取得的成功若干化疗无效（失败）的病例取得明显疗效Iressa,TarcevaNSCLCPtbasedchemoFailureSorafenib,SunibinibRCC,RefractoryGISTGleevecCML,GISTHerceptinHer2(+)BreastCaErbit

8、uxChemo-resi