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作为NSCLC的治疗点,MET的角色在NSCLC及其他疾病中不断变化

Jii Bum Lee¹, Joo Sung Shim², Byoung Chul Cho³

¹Division of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea.

Nature reviews. Clinical oncology

|July 18, 2025

概括

向原瘤基因MET对于治疗各种固体癌症至关重要. 新兴的疗法,如MET氨酸激酶抑制剂,抗体和抗体-药物合物,对MET改变的瘤显示出有前途.

科学领域:

在瘤学瘤学.
分子生物学分子生物学
药物开发药物开发

背景情况:

原型瘤基因MET变化驱动瘤的发展,入侵,并在固体癌症中转移.
可采取行动的MET变化包括MET外显子14跳转 (METex14) 突变,放大,过度表达和融合,在不同类型的瘤中发生率不同.
获得的MET放大/过度表达是常见的,具有显著的临床影响,与较为罕见的de novo变化形成鲜明对比.

研究的目的:

审查针对实体瘤中MET变化的理由.
总结已批准和新兴的MET向疗法的临床疗效和毒性.
讨论对MET改变的固体瘤不断发展的治疗范式.

主要方法:

对MET向药物的临床试验和研究的文献综述.
对MET氨酸激酶抑制剂 (TKIs),抗体和抗体-药物联合体 (ADCs) 的疗效和安全数据的分析.
检查各种固体癌症中不同MET变化的发生率和临床相关性.

主要成果:

METex14突变是非小细胞肺癌 (NSCLC) 中的一个明显的致癌驱动因素.
已批准的MET TKI (capmatinib,tepotinib,savolitinib) 治疗了晚期的METex14突变NSCLC.
新出现的数据支持MET TKIs,抗MET抗体和MET导向的ADC用于NSCLC和其他瘤中的MET放大/过度表达,最近FDA批准了NSCLC中的telisotuzumab vedotin.

结论:

针对MET改变是一个快速发展的领域,有各种不同的治疗策略.
了解各种MET向药物的疗效和毒性概况对于临床实践至关重要.
包括TKI,抗体和ADC在内的MET向疗法为MET改变的实体瘤患者提供了新的治疗选择.

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