药学学报, 2019, 54(8): 1364-1371
王晨, 陈淑珍. 非小细胞肺癌治疗药物EGFR-TKIs获得性耐药机制的研究进展[J]. 药学学报, 2019, 54(8): 1364-1371.
WANG Chen, CHEN Shu-zhen. Advances in the mechanisms of acquired resistance to EGFR-tyrosine kinase inhibitors in non-small cell lung cancer[J]. Acta Pharmaceutica Sinica, 2019, 54(8): 1364-1371.

王晨, 陈淑珍
中国医学科学院、北京协和医学院医药生物技术研究所, 北京 100050
关键词:    非小细胞肺癌      表皮生长因子受体酪氨酸激酶抑制剂      获得性耐药      表皮生长因子受体依赖性      表皮生长因子受体非依赖性     
Advances in the mechanisms of acquired resistance to EGFR-tyrosine kinase inhibitors in non-small cell lung cancer
WANG Chen, CHEN Shu-zhen
Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
Lung cancer ranks the first in the mortality rate among all cancers, and non-small cell lung carcinoma (NSCLC) accounts for about 80% of the incidence of lung cancer. In recent years, the drugs targeting specific molecules have been developed rapidly. The epidermal growth factor receptor-tyrosine kinase inhibitors (EGFRTKIs) have achieved good results in the treatment of patients with NSCLC. Currently, there are three generations of EGFR-TKIs, and the treatment outcome of these drugs surpasses traditional chemotherapies. However, the problems of acquired resistance remains in the course of treatment. In this review, research progress of the mechanisms of acquired resistance is divided into two parts:EGFR-dependent pathway and EGFR-independent pathway. The EGFR-dependent pathway mainly includes EGFR gene mutations, whereas the EGFR-independent pathways include HER2 amplification, BIM deletion, activation of HGF/c-Met pathway, activation of IGF1R, RAS mutation, PTEN deletion, epithelial-mesenchymal transition, PUMA loss, and high levels of expression of VEGF or IL-6. These interconnected mechanisms are linked with acquired resistance to EGFR-TKIs in NSCLC.
Key words:    non-small cell lung cancer    epidermal growth factor receptor-tyrosine kinase inhibitor    acquired resistance    EGFR-dependence    EGFR-independence   
收稿日期: 2019-01-24
DOI: 10.16438/j.0513-4870.2019-0089
基金项目: 国家自然科学基金资助项目(81621064);中国医学科学院医学与健康科技创新工程(2016-I2M-2-002);重大新药创制科技重大专项(2018ZX09711001-007-002).
通讯作者: 陈淑珍,Tel:86-10-63166305,Fax:86-10-63138137,E-mail:bjcsz@imb.pumc.edu.cn
Email: bjcsz@imb.pumc.edu.cn
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