晚期胃肠间质瘤联合靶向药物治疗进展

Research progress in combination targeted therapy for advanced gastrointestinal stromal tumors

胃肠间质瘤(gastrointestinal stromal tumors,GIST)是消化道最常见的间叶源性肿瘤,起源于Cajal间质细胞。所有的GIST均被认为具有一定程度的恶性潜能。KIT/血小板衍生生长因子受体α(platelet-derived growth factor receptor alpha,PDGFRA)基因突变导致的受体酪氨酸激酶编码蛋白异常激活,是目前已知GIST最主要的发病机制。酪氨酸激酶抑制剂(tyrosine kinase inhibitor,TKI)是治疗的主要选择,目前单药TKI序贯治疗是GIST的标准治疗方案,但一线治疗耐药以后,后线治疗的疗效有限。因此,针对不同靶点的药物联合治疗是目前重要的探索方向。在此,本文结合了近年来关于GIST联合靶向治疗的研究进展,包括两种TKI联合治疗、TKI与下游通路抑制剂联合治疗等,旨在对晚期GIST联合治疗的有效性及安全性进行全面的分析和讨论。

Gastrointestinal stromal tumors(GIST)originated from Cajal cells are the most common mesenchymal tumors of the digestive tract.All GISTs are considered to have malignant potential.Abnormal activation of the coding protein of receptor tyrosine kinase caused by mutations in the KIT/platelet-derived growth factor receptor alpha(PDGFRA)gene is the most important pathogenesis of GIST.Tyrosine kinase inhibitor(TKI)targeted therapy is the main treatment choice.Currently,sequential single-agent TKI therapy is the standard treatment for GIST,while after resistance to first-line treatment,the efficacy of late-line therapies is limited.Therefore,combination therapy of drugs acting on different targets is an important exploration direction.Here,this article aims to comprehensively analyze and discuss the efficacy and safety of combination targeted therapy in advanced GIST based on the research progress of GIST combination targeted therapy in recent years,including combination therapies of two TKIs or a TKI and a downstream pathway inhibitor.