【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。更多还原

【Abstract】 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 T790 M 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.更多还原