文档介绍：EGFR-TKI耐药后治疗策略表皮生长因子信号通路EGFR-TKI获得性耐药机制MajorMechanismsofAcquiredResistanceIdentifiedinClinicalSpecimensMechanismEstimatedFrequency(%)icalterationsinEGFRT790Mmutations50D761Y,T854A,andL747Smutations5EGFRamplification8BypasssignalingtractsMETamplification5-22HER2amplification12PIK3CAmutations5BRAFmutations1HGFoverexpression1of2casesPhenotypicalterationsTransformationtosmall-celllungcancer3-14ALK–icalterationsinALK所占比例%ALKsecondarymutations(eg,L1196M)22-36ALKgeneamplification7-18BypasssignalingtractsEGFRactivation44KITgeneamplification15Abbreviations:EGFR,epidermalgrowthfactorreceptor;TKI,tyrosinekinaseinhibitor;HER2,humanepidermalgrowthfactorreceptor2;HGF,hepatocytegrowthfactor;ALK,:单药用于晚期治疗无法根治疾病分期药物中位TTP参考文献CML原始细胞危象伊马替尼~10月Sawyersetal,2002(‘缓解持续’)GIST晚期伊马替尼~17月Heinrichetal,2004(‘无事件生存’)肺癌晚期吉非替尼/厄洛替尼~9-10月Mitsudomietal,2009Roselletal,2012肺癌晚期克唑替尼~10月Camidgeetal,2011黑色素瘤晚期Vemurafenib~al,2012重复活检:观察越多,,Adapted;Sequist,(RECIST标准)肿瘤评价SD(大于6个月)肿瘤评价CR或PRJackmanDMetal;;28(2):357-(monotherapy).,L858R,(6months):EGFR,epidermalgrowthfactorreceptor;TKI,:现有的治疗模式如何处理TKI继发性耐药? (Continuoustreatmentbeyondprogression)