基因融合介导EGFR-TKI获得性耐药  

Gene Fusions as Acquired Resistance Mechanisms of EGFR-TKI

作　　者：邵宜[1] 钟殿胜[1] Yi SHAO;Diansheng ZHONG(Department of Medical Oncology,Tianjin Medical University General Hospital,Tianjin 300052,China)

机构地区：[1]天津医科大学总医院肿瘤内科,天津300052

出　　处：《中国肺癌杂志》2020年第5期381-387,共7页Chinese Journal of Lung Cancer

基　　金：天津市自然科学基金(No.18JCQNJC12700)资助。

摘　　要：具有表皮生长因子受体(epidermal growth factor receptor, EGFR)敏感突变的非小细胞肺癌患者对酪氨酸激酶抑制剂(tyrosine kinase inhibitors, TKIs)反应良好,但是最终会发生获得性耐药。近来发现EGFR-TKIs耐药机制除了EGFR二次突变、MET扩增、组织学转化等外,基因融合的出现也可以介导TKIs耐药。TKIs耐药后可发生转染重排基因(rearranged during transfection, RET),鼠类肉瘤病毒癌基因同源物B1(v-raf murine sarcoma viral oncogene homolog B1, BRAF),间变性淋巴瘤激酶(anaplastic lymphoma kinase, ALK)等多种基因融合,发生率约为1%左右。临床病例及体内体外实验证实基因融合可以介导EGFR-TKI耐药,联合使用EGFR抑制剂和基因融合抑制剂可能是一种有效的治疗方式。对基因融合介导EGFR-TKI耐药的理解有助于后续诊疗策略的制定。Patients with sensitive epidermal growth factor receptor(EGFR) mutations often respond to tyrosine kinase inhibitors(TKIs), but acquired resistance will eventually develop. The most common mechanisms of acquired resistance include secondary EGFR mutation, MET amplification, and histologic transformation. Besides, gene fusions could also mediate the process of acquired resistance. Various gene fusions including rearranged during transfection(RET), v-raf murine sarcoma viral oncogene homolog B1(BRAF) and anaplastic lymphoma kinase(ALK) could take place after TKIs resistance, the incidence of which is around 1%. The clinical cases and experiments both in vitro and in vivo have proved the role of gene fusions in EGFR-TKI resistance. The combination of EGFR inhibitors and gene fusion inhibitors might be an effective therapeutic method. The understanding of gene fusions at EGFR-TKI resistance may contribute to the subsequent diagnosis and treatment strategy.

关 键 词：肺肿瘤 表皮生长因子受体 基因融合 获得性耐药 

分 类 号：R734.2[医药卫生—肿瘤]