奥希替尼治疗非小细胞肺癌患者的耐药机制研究进展

Research progress on the drug resistance mechanism of Osimertinib in patients with non-small cell lung cancer

奥希替尼是第三代表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKIs)。目前被批准用于EGFR突变晚期非小细胞肺癌(NSCLC)患者的一线治疗及第一代EGFR-TKIs治疗进展后伴有T790M突变NSCLC的二线治疗。临床研究显示,奥希替尼能够明显改善NSCLC患者的无进展生存期(PFS),但同时也带来了严重的耐药问题。近年来研究发现,一线应用奥希替尼的耐药机制主要有依赖EGFR通路、旁路信号通路的激活;二线及二线后应用奥希替尼所产生的耐药机制有依赖EGFR通路、旁路信号通路的激活,细胞表型转化。不同的用药时间产生的耐药机制有所不同。本文将从临床用药时间角度对奥希替尼耐药机制及治疗策略进行综述,以期为防治或延缓奥希替尼耐药提供理论依据。

Osimertinib is a third-generation epidermal growth factor receptor-tyrosine kinase inhibitors(EGFR-TKIs).It is currently approved for first-line treatment of patients with advanced non-small cell lung cancer(NSCLC)with EGFR mutation and second-line treatment with T790M mutant NSCLC after the first-generation EGFR-TKIs treatment progresses.Clinical studies have shown that Osimertinib can significantly improve the progression-free survival(PFS)of NSCLC patients,but it also brings serious drug resistance problems.In recent years,studies have found that the first-line application of Osimertinib resistance mechanism mainly depends on the activation of EGFR pathway and bypass signaling pathway;the drug resistance mechanism produced by the second-line and second-line application of Osimertinib depends on the activation of the EGFR pathway,the bypass signaling pathway,and the transformation of the cell phenotype.Osimertinib has different drug resistance mechanisms at different times.In order to provide a theoretical basis for the prevention and treatment of Osimertinib resistance,this article will review the different drug resistance mechanisms and treatment strategies of Osimertinib from the perspective of clinical drug use time.