脑胶质瘤中的MET基因变异及其作为治疗 靶点的临床实践  

Genomic alterations of MET and the clinical practice of treatment targeting MET in glioma

作　　者：胡慧敏 刘彦伟[1] 黄利杰 江涛[1] Hu Huimin;Liu Yanwei;Huang Lijie;Jiang Tao(Beijing Neurosurgical Institute,Beijing Tiantan Hospital,Capital Medical University,Beijing 100070,China)

机构地区：[1]北京市神经外科研究所,首都医科大学附属北京天坛医院,100070

出　　处：《神经疾病与精神卫生》2021年第5期305-309,共5页Journal of Neuroscience and Mental Health

基　　金：国家自然科学基金(81761168038,81972816,81702460);北京博士后研究基金(2020-ZZ-009)。

摘　　要：脑胶质瘤是一种难治性的颅内原发恶性肿瘤,肝细胞生长因子(HGF)的过表达、MET基因扩增或突变均会导致MET通路的异常激活。作为经典癌症通路,MET通路的高度激活会促进胶质瘤细胞的增殖、迁移及血管生成和其他肿瘤微环境因素的变化,最终导致肿瘤恶性进展或治疗抵抗。基于对MET基因变异及MET通路在脑胶质瘤发生及进展中重要作用的研究和认识,靶向MET通路的抗癌药物被视为脑胶质瘤治疗最有潜力的发展方向之一。目前,已有多种MET靶向药物被成功研发,并开展了多项针对脑胶质瘤适应证的临床试验。现对脑胶质瘤中MET基因变异的发生特点和作用及MET靶向治疗药物的临床试验进行述评。Glioma is a kind of refractory primary intracranial malignant tumor.Overexpression of hepatocyte growth factor(HGF)and amplification or mutation of MET gene will both lead to abnormal activation of MET pathway.Hyperactivation of MET pathway,the canonical oncogenic pathway,promotes the proliferation,migration,angiogenesis and other tumor microenvironment factors of glioma cells,and eventually lead to malignant progression or therapeutic resistance.Based on the research and understanding of MET gene alterations and the important role of MET pathway in the development and progression of glioma,anticancer drugs targeting MET pathway are regarded as one of the most promising development directions of glioma therapy.Currently,a variety of drugs targeting MET had been successfully developed and several clinical trials had been proposed for application of these drugs in glioma treatment.This paper reviews the characteristics and role of MET alterations in glioma,as well as clinical trials of drugs targeting MET pathway.

关 键 词：脑胶质瘤 MET基因变异 MET抑制剂 临床试验 

分 类 号：R739.41[医药卫生—肿瘤]