摘要
奥希替尼是一种不可逆第三代表皮生长因子受体(EGFR)酪氨酸激酶抑制剂(TKI),对EGFR敏感突变和T790M突变具有高度选择性.尽管第三代EGFR-TKI治疗非小细胞肺癌(NSCLC)患者取得了良好疗效,但耐药的发生不可避免.耐药机制影响了后续治疗方案的制定,精准靶向耐药机制,实施个体化治疗方案更有助于患者临床获益.第三代EGFR-TKI获得性耐药机制主要包括EGFR依赖的耐药机制、旁路替代途径激活及表型转化.部分耐药机制已有较为明确的治疗方式,但更多耐药机制的克服策略尚在探索之中.文章旨在综述第三代EGFR-TKI治疗NSCLC后的获得性耐药机制及克服策略,发现潜在临床靶点.
Osimertinib is an irreversible,third-generation epidermal growth factor receptor(EGFR)tyrosine kinase inhibitor(TKI)that is highly selective for EGFR sensitizing mutations as well as T790M mutation.Despite third-generation EGFR-TKIs having achieved good efficacy in the treatment of non-small cell lung cancer(NSCLC),patients inevitably develop resistance.Resistance mechanisms of EGFR-TKI might affect the follow-up therapeutic regimen.Precisely targeting drug resistance mechanisms and implementing individualized treatments can gain more clinical benefits.
作者
高茹云
谢同济
韩晓红
石远凯
Gao Ruyun;Xie Tongji;Han Xiaohong;Shi Yuankai(Department of Medical Oncology,National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs,Beijing 100021,China;Clinical Pharmacology Research Center,Peking Union Medical College Hospital,State Key Laboratory of Complex Severe and Rare Diseases,NMPA Key Laboratory for Clinical Research and Evaluation of Drug,Beijing Key Laboratory of Clinical PK&PD Investigation for Innovative Drugs,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing 100730,China)
出处
《中国肿瘤临床与康复》
2023年第6期353-362,共10页
Chinese Journal of Clinical Oncology and Rehabilitation
基金
国家自然科学基金(81972805)
国家科技重大专项“重大新药创制”(2017ZX09304015)
中国医学科学院肿瘤医院肿瘤内科重点学科研究基金(CICAMSM0MP2022006)。
关键词
非小细胞肺癌
第三代表皮生长因子酪氨酸激酶抑制剂
奥希替尼
耐药
Non-small cell lung cancer
Third-generation epidermal growth factor receptor
Tyrosine kinase inhibitor
Osimertinib
Drug resistance
