Ni Lianfang, Nie Ligong
Department of Geriatric Medicine, Peking University First Hospital, 100034 Beijing, China.
Department of Respiratory and Critical Care Medicine, Peking University First Hospital, 100034 Beijing, China.
Zhongguo Fei Ai Za Zhi. 2018 Feb 20;21(2):110-115. doi: 10.3779/j.issn.1009-3419.2018.02.02.
Targeted therapy of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKIs) has been the standard modality as first-line treatment of advanced EGFR-mutated non-small cell lung cancer (NSCLC). The third-generation EGFR-TKIs has been approved to overcome the EGFR T790M mutation in patients resistant to the first-or second-generation TKIs, which brings more survival benefits for patients with advanced NSCLC. Unfortunately, acquired resistance inevitably develops after application of approximately 10 months. Heterogeneities of the tumor determines the diversity of resistance. Mechanisms of resistance to the third-generation TKIs includs EGFR-dependent pathway (such as new EGFR mutations, T790M reduction/disappearance and EGFR amplification, etc.) and EGFR-independent pathway (such as bypass pathway activation and histological transformation, etc.). In this paper, we reviewed principle mechanisms of acquired resistance to third-generation EGFR-TKIs.
表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKIs）靶向治疗已成为晚期EGFR突变非小细胞肺癌（NSCLC）一线治疗的标准模式。第三代EGFR-TKIs已被批准用于克服对第一代或第二代TKIs耐药患者的EGFR T790M突变，这为晚期NSCLC患者带来了更多生存益处。不幸的是，在应用约10个月后不可避免地会出现获得性耐药。肿瘤的异质性决定了耐药的多样性。第三代TKIs的耐药机制包括EGFR依赖性途径（如新的EGFR突变、T790M减少/消失和EGFR扩增等）和EGFR非依赖性途径（如旁路途径激活和组织学转化等）。在本文中，我们综述了第三代EGFR-TKIs获得性耐药的主要机制。
