胃肠道间质瘤分子靶向治疗的研究进展

Progress in molecular targeting therapy for gastrointestinal stromal tumors

胃肠道间质瘤(gastrointestinal stromal tumor, GIST)是最常见的腹部软组织恶性肿瘤,来源于卡哈尔(Cajal)间质细胞或共同的前体细胞,由突变的KIT基因或血小板源性生长因子受体α(PDGFRα)基因驱动,均表达Ⅲ型酪氨酸激酶受体。酪氨酸激酶受体抑制剂伊马替尼用于晚期GIST的治疗取得了卓越的疗效,使得GIST成为实体肿瘤靶向药物治疗最成功的范例之一。之后随着对GIST分子生物学研究的日益深入,在精准医疗时代背景下,GIST的分子靶向治疗从晚期一线、二线、三线治疗到术后辅助治疗、术前治疗均有了清晰的脉络,从而为GIST患者提供了显著的生存获益。本文从晚期GIST到早期GIST的术前、术后分子靶向治疗进行了系统而全面的梳理,并分析问题、提出解决对策及对未来的展望,旨在为GIST临床分子靶向药物治疗提供参考。

Gastrointestinal stromal tumors(GISTs)are the most common malignant tumor of abdominal soft tissue.It originates from Cahal(Cajal)interstitial cells or common precursor cells,and is driven by the mutated KIT gene or platelet-derived growth factor receptor alpha(PDGFRa)gene,all expressing typeⅢtyrosine kinase receptors.Imatinib mesylate,a tyrosine kinase receptor inhibitor,has been used for the standard treatment of advanced GIST,which has achieved remarkable results.Thus,GIST has become the most successful example of target therapy for solid tumors.In the context of the era of precision medicine,with the deepening in research of GISTs molecular biology,the molecular targeted treatment of GISTs has obtained a clear venation from the first-line,second-line and third-line of the advanced stage to the postoperative auxiliary and preoperative treatment,providing significant survival benefits for GISTs patients.This article systematically and comprehensively combed the preoperative and postoperative molecular targeting therapy from advanced GIST to early GIST,and analyzed the problems,proposed solutions and prospects for the future,aiming to provide reference for clinical application of molecular targeting drug therapy for GIST.