第三代EGFR-TKIs耐药之初探  

Mechanisms of Resistance to the Third-generation Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors in Non-small Cell Lung Cancer

作　　者：倪莲芳[1] 聂立功[2] Lianfang NI;Ligong NIE(Department of Geriatric Medicin;Department of Resplratory and Critical Care Medicine, Peking University First Hospital, 100034 Beijing, Chin)

机构地区：[1]北京大学第一医院老年内科,北京100034 [2]北京大学第一医院呼吸和危重症科,北京100034

出　　处：《中国肺癌杂志》2018年第2期110-115,共6页Chinese Journal of Lung Cancer

摘　　要：表皮生长因子受体酪氨酸激酶抑制剂(epidermal growth factor receptor-tyrosine kinase inhibitors,EGFRTKIs)靶向治疗已成为EGFR基因突变晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)患者的一线治疗方法。第三代EGFR-TKIs用于一、二代TKIs耐药EGFR T790M突变NSCLC的治疗,给晚期肺癌患者带来更多的生存获益。然而,第三代EGFR-TKIs应用一段时间后不可避免地会出现耐药。肿瘤的异质性决定了耐药机制的多样性,第三代EGFR-TKIs的耐药包括依赖EGFR通路(新发突变、T790M减少或消失和EGFR基因扩增等)和不依赖EGFR通路(旁路途径的激活和细胞表型的转变)两大类,现就此问题进行简单的综述。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 mu- tations, T790M reduction/disappearance and EGFR amplification, etc.） and EGFR-independent pathway （such as bypass path- way activation and histological transformation, etc.）. In this paper~ we reviewed principle mechanisms of acquired resistance to third-generation EGFR-TKIs.

关 键 词：EGFR受体 肺肿瘤 第三代EGFR-TKIs 耐药 

分 类 号：R734.2[医药卫生—肿瘤]