Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China.
Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, 510060, China.
Curr Treat Options Oncol. 2020 Apr 18;21(4):33. doi: 10.1007/s11864-020-0723-5.
The MET exon 14 skipping mutation is found in approximately 3% of lung adenocarcinomas and slightly more than 2% of lung squamous cell carcinomas. In recent years, more and more evidence has shown that MET inhibitors have achieved good anti-tumor effect in patients with MET exon 14 skipping mutation, suggesting that MET exon 14 skipping mutation may be a new target for NSCLC patients. Patients with positive MET exon 14 skipping mutation are recommended to be administered MET inhibitors, and crizotinib is recommended by the NCCN guideline. Due to the presence of gene amplification, second site mutation, bypass activation, and pathological type transformation, one of the inevitable problems of targeted therapy is drug resistance. If type I MET inhibitors (crizotinib, capmatinib, tepotinib, savolitinib) drug resistance is developed, type II MET inhibitors (cabozantinib, glesatinib, merestinib) can be considered.
MET 外显子 14 跳跃突变约占肺腺癌的 3%,略高于肺鳞癌的 2%。近年来,越来越多的证据表明,MET 抑制剂在 MET 外显子 14 跳跃突变的患者中取得了良好的抗肿瘤效果,这表明 MET 外显子 14 跳跃突变可能是 NSCLC 患者的一个新靶点。建议对 MET 外显子 14 跳跃突变阳性的患者进行 MET 抑制剂治疗,NCCN 指南推荐使用克唑替尼。由于存在基因扩增、第二部位突变、旁路激活和病理类型转化,靶向治疗不可避免的问题之一是耐药性。如果出现 I 型 MET 抑制剂(克唑替尼、卡马替尼、特泊替尼、 savolitinib)耐药,可以考虑使用 II 型 MET 抑制剂(卡博替尼、吉列替尼、merestinib)。