《肺癌的靶向治疗》PPT课件

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1、肺癌的靶向治疗北京协和医院呼吸内科李龙芸中国肺癌流行病学回顾26.9%38.4%30.5%2000和2005年肺癌患者数Yangetal,2005患者数晚期肺癌的化学治疗已达平台化学治疗是肺癌的主要治疗方法一线中位生存期8~10个月一年存活率30%~40%二线中位生存期5~7个月21世纪分子靶向治疗飞越进展为肺癌病人带来了新生的希望新的靶向治疗药物肿瘤细胞靶的选择毒性小药物生物活性高治疗后能提高生活质量经选择性的病人能获得很好的疗效TargetedCancerTherapiesTargetingTumor&ItsmicroenvironmentEndothelialCellCanc

2、erCellGrowthfactorsignalingMicrotubuledynamicsHistoneacetylation/deacetylationDNAreplication,transcription,repairMetastasis1143211425TumorCellGrowth/ReplicationAngiogenesisTargetsofCancerTherapyCellGrowthMotilitySurvivalProliferationAngiogenesisPPPPPDK1,2GrowthFactorSignalingGeneTranscriptio

3、nDNAReplicationandRepair16358910112PlasmaMembraneNuclearMembrane1274771.Growthfactors2.Growthfactorreceptors3.Adaptorproteins4.Dockingproteins/bindingproteins5.Guaninenucleotideexchangefactors6.Phosphatasesandphospholipases7.Signalingkinases8.Ribosomes9.Transcriptionfactors10.Histones11.DNA12.

4、MicrotubulesMicrotubuleDynamicsRNATranslationCellGrowth,Proliferation,Survival,TransformationProliferationMigrationGrb2GlycogenSynthesisSurvivalAkt/PKBMEKERKPI3-KRAFPI(4,5)P2PI(3,4,5)P3PTENPPPPEGF,TGF-αEGFRHER2PDK1,2PDK1,2RAS-GTPSOSGTPPRAS-GDPTKIGrowthFactorSignalingThroughEGFR/HER2ReceptorTyr

5、osineKinase(RTK)FamiliesandTheirActivationIGF-1RPPPPHER2HER3HER4EGFRTGF-aEGFHeregulinEpiregulinHeregulinEpiregulinNoneHER(erbB)FamilyVEGFR-2VEGFR-3VEGFR-1VEGF-AVEGF-BVEGF-CVEGF-DVEGFRFamilyFlt-3PDGFRKITFLPDGFSCFPDGFRFamilyPPPPVEGFRs,PDGFR,KIT,Flt-3MutantFlt-3PPPPEGFR/HER2PPPPReceptorDimerizati

6、onandActivationVEGF-AVEGF-CVEGF-DIGF-1IGF-2目前的靶向治疗药物-1EGFR抑制剂EGFRErlotinib(厄罗替尼)(Ⅲ)Gefitinib(吉非替尼、ZD1839)(Ⅲ)Cetuximab(ErbituxMoAbs西妥昔单抗)Her-2Trastuzumab(曲妥珠单抗)(Ⅱ)EGFR+Her-2BIBW2992(TOVOK)目前的靶向治疗药物-2血管生长抑制剂VEGFbevacizumab（贝伐单抗）（Ⅲ）thalidomide（沙利度胺）（Ⅲ）Vandetanib(范得他尼、ZD6474、ZACTIMA)（Ⅲ）Cediranib(R

7、ecentin,AZD2171)（Ⅲ）Axitinib(艾斯替尼、AG-013736)（Ⅲ）MMP(基质性金属蛋白酶抑制剂)Prinomastat(司立马司他)（Ⅲ）UnclearEndostatin(血管内皮抑制素)（Ⅲ）目前的靶向治疗药物-3诱导细胞凋亡Bc1-2oblimerser(G3139、奥利默森纳)(Ⅰ)XIAPAEG35156(Ⅰ)SurvivinISIS23722(Ⅰ)其它FarnesyltransferaseLonafarnib(Ⅲ)Proteos