摘要
MET蛋白是一种细胞表面受体酪氨酸激酶,主要在上皮细胞中表达。在结合其唯一已知的配体肝细胞生长因子 (HGF) 后,MET 同源二聚化、磷酸化并刺激细胞内信号传导以驱动细胞增殖。在各种癌症类型中经常观察到 MET 的扩增或过度活化,它与对常规和靶向化疗的不良反应有关。最近,新出现的证据还表明,MET/HGF 信号传导可能发挥免疫抑制作用,并可能赋予对癌症免疫治疗的抗性。在这篇综述中,我们总结了 MET 在常规化疗、靶向治疗和免疫治疗耐药中的作用的临床前和临床证据。以前在未选择或 MET 过度表达的癌症中研究 MET 靶向治疗的临床试验大多产生了不利的结果。最近关注 MET 外显子 14 改变和 MET 扩增的临床研究对 MET 抑制剂治疗产生了令人鼓舞的治疗反应。讨论了 MET 抑制剂治疗克服癌症患者耐药性的转化相关性。
关键词: 癌症免疫治疗、耐药性、肝细胞生长因子、MET扩增、MET抑制剂、酪氨酸激酶。
图形摘要
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