消化道肿瘤中的肝细胞生长因子受体信号靶向治疗研究进展

摘要

Hepatocyte growth factor receptor (c-Met) signaling plays an important role in promoting tumor cell proliferation,metastasis,invasion and tumor angiogenesis.Aberrant activation of c-Met signaling is shown to be associated with a number of gastrointestinal carcinomas.c-Met targeted therapy has become a hot spot in anti-tumor therapy,but many tumors develop resistance to the drugs.The molecular mechanisms of resistance include c-Met itself or downstream signaling protein gene mutation,bypass compensation mechanism of other membrane receptor signaling and non-specific inhibition of neutrophils c-Met signaling.With the improvement of biotechnology,antibody-drug conjugates,bispecific antibody and CAR-T cell therapy gradually become new methods for targeted therapy.This paper reviewed the c-Met signaling pathway,c-Met inhibitors,resistance of c-Met inhibitors and new methods of targeted therapy.%肝细胞生长因子受体(c-Met)信号在促进肿瘤细胞增殖、转移、侵袭和肿瘤血管生成中扮演重要的角色.多种消化系统肿瘤被证实与c-Met的异常表达相关.c-Met靶向治疗成为抗肿瘤治疗中的一大热点,但c-Met抑制剂耐药性普遍存在,其分子机制包括c-Met本身或下游信号蛋白的基因突变、其他膜受体信号的旁路补偿机制、中性粒细胞c-Met信号的非特异性抑制.随着生物技术的进步,抗体-药物偶联物、双特异性抗体及CAR-T细胞治疗逐渐成为肿瘤靶向治疗的新手段.本文对消化道肿瘤靶向治疗中的c-Met信号通路、c-Met抑制剂、c-Met抑制剂耐药性及靶向治疗的新手段作一概述.