第三代EGFR-TKIs在非小细胞肺癌中的耐药机制及应对策略

The resistance mechanism and coping strategy of the third-generation EGFR-TKIs in NSCLC

表皮生长因子受体酪氨酸激酶抑制剂(epidermal growth factor receptor tyrosine kinase inhibitors,EGFR-TKIs)靶向治疗相对于传统化疗具有很大的优势,已成为晚期非小细胞肺癌EGFR敏感突变患者的一线治疗方案。然而,耐药现象不可避免地发生。EGFR第20号外显子的T790M突变是第一、二代EGFRTKIs的主要耐药机制。第三代EGFR-TKIs,如AZD9291、CO-1686等可克服T790M耐药,并在临床试验中显示出良好的治疗效果,然而,第三代EGFR-TKIs的耐药同样不可避免,该文就第三代EGFR-TKIs的耐药机制及目前的应对策略进行综述。

Epidermal growth factor receptor tyrosine kinase inhibitors （EGFR-TKIs） targeted therapy has great advantages compared to conventional chemotherapies and has become the first-line treatment of EGFR sensitive mutations in patients with advanced non-small cell lung cancer. However, the development of acquired drug resistance is inevitable. EGFR T790M mutation is the main mechanism of the first and second generation EGFR-TKIs. The thirdgeneration EGFR-TKIs including AZD9291 and CO-1686 showed favorable treatment effect in clinical trials. However, resistance problems appeared soon. This review summarized the resistance mechanisms of the third-generation EGFRTKIs and the potential coping strategy.