表皮生长因子受体抑制剂耐药机制的研究进展

表皮生长因子受体(EGFR)是抗肿瘤治疗中重要的分子靶点,两类抗表皮生长因子受体(anti-EGFR)药物:单克隆抗体及小分子酪氨酸激酶抑制剂已成功应用于临床,但其原发和继发耐药问题也日益受到关注。肿瘤对anti-EGFR药物耐药的可能机制包括:EGFR、K-ras、Braf突变;配体的自分泌或旁分泌;原癌基因MET扩增;下游通路持续活化;激活替代通路;肿瘤诱导不依赖于EGFR活化的血管生成等。

Research Progress of Mechanism of Resistance to EGFR Inhibitors

The epidermal growth factor receptor(EGFR)is an important molecular target in cancer treatment,and two classes of anti-EGFR agents,the monoclonal antibodies and the small molecular tyrosine kinase inhibitors,have developed in clinical successfully.Howeverthe primary and secondary resistance to anti-EGFR agents have been paid increasing attention.The mechanisms of resistance to EGFR inhibitors in solid tumors may include:EGFR,K-ras,Braf mutations;autocrine/paracrine production of ligand;MET amplification;constitutive activation of a downstream pathway;activation of alternative pathways;activation of EGFR-independent,tumour-induced angiogenesis and etc..