Shao Yi, Zhong Diansheng
Department of Medical Oncology, Tianjin Medical University General Hospital, Tianjin 300052, China.
Zhongguo Fei Ai Za Zhi. 2020 May 20;23(5):381-387. doi: 10.3779/j.issn.1009-3419.2020.101.04.
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.
具有敏感表皮生长因子受体（EGFR）突变的患者通常对酪氨酸激酶抑制剂（TKIs）有反应，但最终会产生获得性耐药。获得性耐药最常见的机制包括继发性EGFR突变、MET扩增和组织学转化。此外，基因融合也可介导获得性耐药过程。多种基因融合，包括转染重排（RET）、v-raf鼠肉瘤病毒癌基因同源物B1（BRAF）和间变性淋巴瘤激酶（ALK），可在TKIs耐药后发生，其发生率约为1%。临床病例以及体外和体内实验均证实了基因融合在EGFR-TKI耐药中的作用。EGFR抑制剂与基因融合抑制剂联合使用可能是一种有效的治疗方法。了解EGFR-TKI耐药时的基因融合情况可能有助于后续的诊断和治疗策略制定。
