第三代EGFR酪氨酸激酶抑制剂在非小细胞肺癌临床治疗中的应用及研究进展  

Advances in the research and clinical application of the third generation EGFR TKIs in the treatment of non-small cell lung cancer

作　　者：张可心 贾文静 崔佳文 敖路遥 周芳[1] 王广基[1] 刘嘉莉[1] ZHANG Kexin;JIA Wenjing;CUI Jiawen;AO Luyao;ZHOU Fang;WANG Guangji;LIU Jiali(Key Lab of Drug Metabolism and Pharmacokinetics,China Pharmaceutical University,Nanjing 210009,Jiangsu,China)

机构地区：[1]中国药科大学药物代谢动力学重点实验室,江苏南京210009

出　　处：《中国临床药理学与治疗学》2022年第9期1016-1030,共15页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：国家自然科学基金面上项目(82173882);江苏省前沿引领技术基础研究专项(BK20192005)。

摘　　要：表皮生长因子受体(EGFR)是非小细胞肺癌(NSCLC)靶向治疗最重要的靶点之一。目前,靶向EGFR突变的酪氨酸激酶抑制剂(TKIs)已发展至第三代,广泛用于治疗伴有EGFR敏感突变和伴有EGFR T790M耐药突变的NSCLC患者。然而,第三代EGFR TKIs用药过程中不可避免地会出现继发耐药,限制了该类药物的长期使用和临床治疗预后。本文首先围绕已上市或处于临床研究的第三代EGFR TKIs,重点综述了它们的作用特点和临床疗效。其次,从EGFR依赖性耐药和EGFR非依赖性耐药两个方面,归纳了第三代EGFR TKIs发生继发耐药的潜在机制。最后,针对EGFR依赖性耐药、EGFR非依赖性耐药和机制不明确的耐药,分别总结了可能有效的后续用药策略,以期为以EGFR为靶点的药物开发和临床应用提供借鉴和参考。Epidermal growth factor receptor(EGFR)is one of the most common targeted oncogenes in non-small cell lung cancer(NSCLC).The third-generation EGFR tyrosine kinase inhibitors(TKIs)have become the standard treatment for metastatic or recurrent NSCLC patients harboring EGFR positive or concomitant T790M mutations.However,the inevitable emergence of acquired resistance markedly limits their prolonged clinical benefits,although the third-generation EGFR TKIs have shown potent clinical outcomes in initial several months.This paper firstly reviews the characteristics and clinical efficacy of the third-generation EGFR TKIs in the market or in the clinical development.Then this article summarizes the detailed mechanisms behind the acquired drug resistance of third-generation EGFR TKIs,and further expounds the current treatment strategies to overcome the resistance.Collectively,this review could provide more information for the development and clinical application of drugs targeting EGFR.

关 键 词：非小细胞肺癌 酪氨酸激酶抑制剂 EGFR T790M突变 治疗耐药 

分 类 号：R734[医药卫生—肿瘤]