摘要
晚期胃癌(advanced gastric cancer,AGC)包括局部不可切除胃癌(gastric cancer,GC)、转移性GC和术后复发性GC,由于患者诊断延迟且AGC尚缺乏有效治疗方法,因此患者中位生存期仅为6~12个月。目前AGC的主要治疗目标是改善患者症状和延长序贯化疗患者的生存期。虽然全身治疗对AGC的治疗效果逐渐显现,但患者预后远未达到预期。此外,靶向治疗及新型免疫治疗存在耐药发生率高、毒副作用大、患者经济负担重等缺点。因此,寻找新的治疗靶标并研发抗肿瘤药物是一个亟待解决的关键问题。据报道,肝细胞生长因子(hepatocyte growth factor,HGF)/细胞间质上皮转换因子(cellular-mesenchymal epithelial transition factor,c-MET)通路异常激活在GC进展和多线耐药的发生中起到关键作用,可能是GC有潜力的治疗靶点。近年来,一些靶向HGF/c-MET的小分子酪氨酸激酶抑制剂(tyrosine kinase inhibitor,TKI)在GC的治疗中观察到较好的临床效果。同时,新型HGF/c-MET抑制剂(如单克隆抗体、双特异性抗体和抗体偶联药物等)在临床前研究中均表现出较好的抗肿瘤活性,但均处于临床研究的不同阶段,其疗效和安全性仍有待进一步证实。本文阐述HGF/c-MET抑制剂在AGC治疗中的最新研究进展,并讨论HGF/c-MET抑制剂在GC治疗中产生耐药的主要原因及应对策略,旨在为AGC的治疗提供更好的指导并为未来研究提供参考。
Advanced gastric cancer(AGC)includes locally unresectable gastric cancer(GC),metastatic GC,and postoperative recurrent GC.Due to delayed diagnosis and lack of effective treatment for AGC,the median survival time of AGC patients is only 6-12 months.At present,the main treatment goal of AGC is to improve symptoms and prolong the survival time of patients receiving sequential chemotherapy.Although the therapeutic effect of systemic therapy on AGC is gradually becoming apparent,the patient's prognosis is far from expected.In addition,targeted therapy and novel immunotherapy have drawbacks such as high incidence of drug resistance,high toxic side effects,and heavy economic burden on patients.Therefore,finding new therapeutic targets and developing anti-tumor drugs is a key issue that urgently needs to be addressed.According to reports,abnormal activation of the hepatocyte growth factor(HGF)/cellular-mesenchymal epithelial transition factor(c-MET)pathway plays a crucial role in the progression of GC and the occurrence of multi-line resistance and may be a potential therapeutic target for GC.In recent years,some HGF/c-MET-targeting small molecule tyrosine kinase inhibitors(TKIs)have been found to show good clinical effects in the treatment of GC.Meanwhile,new HGF/c-MET inhibitors(such as monoclonal antibodies,bispecific antibodies,antibody drug conjugates,etc.)have shown good anti-tumor activity in preclinical studies,but they are all at different stages of clinical research,and their efficacy and safety still need further confirmation.This review elaborates on the latest research progress of HGF/c-MET inhibitors in the treatment of AGC and discusses the main reasons and strategies for drug resistance,aiming to provide better guidance for the treatment of AGC and provide reference for future research.
作者
石嘉琪
徐洋
郭佩佩
李斌
卢利霞
郑英
李初谊
于晓辉
陈嘉屿
SHI Jiaqi;XU Yang;GUO Peipei;LI Bin;LU Lixia;ZHENG Ying;LI Chuyi;YU Xiaohui;CHEN Jiayu(School of Traditional Chinese and Western Medicine,Gansu University of Chinese Medicine,Lanzhou 730000,Gansu Province,China;Department of Gastroenterology,The 940 Hospital of Joint Logistics Support Force of People's Liberation Army of China,Lanzhou 730050,Gansu Province,China;Basic Medical Laboratory of The 940 Hospital of the Joint Logistics Support Force of the People's Liberation Army of China,Key Laboratory of Stem Cells and Genetic Drugs of Gansu Province,Lanzhou 730050,Gansu Province,China;The Second Hospital of Lanzhou University,Lanzhou 730050,Gansu Province,China)
出处
《肿瘤》
CAS
2024年第2期201-214,共14页
Tumor
基金
甘肃省科技计划项目(20JR10RA017,21JR7RA017)
作者简介
通信作者:于晓辉,E-MAIL:yuxiaohui528@126.com;通信作者:陈嘉屿,E-MAIL:chenjiayu65@163.com
