ALK抑制剂在NSCLC中的耐药机制及逆转策略的研究进展  

Research progress of the resistance mechanism and reversal strategies of ALK inhibitors in NSCLC

作　　者：张迪 冉冬芝 余瑜[1] 甘宗捷[1] ZHANG Di;RAN Dongzhi;YU Yu;GAN Zongjie(School of Pharmacy,Chongqing Medical University,Chongqing 400016;Chongqing Institute for Food and Drug Control,Chongqing 401121,China)

机构地区：[1]重庆医科大学药学院,重庆400016 [2]重庆食品药品检验检测研究院,重庆401121

出　　处：《中国药科大学学报》2020年第6期655-663,共9页Journal of China Pharmaceutical University

基　　金：国家自然科学基金资助项目(No.21907013);重庆市教委科学技术研究资助项目(No.KJQN201900431)。

摘　　要：间变性淋巴瘤激酶(ALK)抑制剂是目前治疗NSCLC伴ALK阳性的有效药物,然而,耐药性的产生严重限制了其临床应用。本文对ALK抑制剂耐药产生的主要机制如二次基因突变、基因扩增、旁路通路激活等进行了简要介绍,并对联合用药、开发新型PROTAC降解剂等逆转耐药策略进行了综述,以期为ALK抑制剂药物的未来发展提供参考。Anaplastic lymphoma kinase(ALK)inhibitors are regarded as effective drugs for the treatment of ALK-positive NSCLC.However,the emergence of drug resistance has limited its further clinical application.This article briefly introduces the resistance mechanism of ALK inhibitors including acquired secondary muta⁃tions,gene amplification,bypass signaling pathway activation and reviews the recent advances on the reversal strat⁃egies such as drug combination,developing novel PROTACs to overcome drug resistance,so as to provide some reference for the development of ALK inhibitors.

关 键 词：非小细胞肺癌 ALK抑制剂 耐药 逆转策略 进展 

分 类 号：R914[医药卫生—药物化学]