胃肠间质瘤分子发病机制及精准治疗研究进展  

Research progress on the molecular pathogenesis and precise therapy of gastrointestinal stromal tumors

作　　者：吴昀紫 魏千 马亮亮 丁世康 解亦斌 Wu Yunzi;Wei Qian;Ma Liangliang;Ding Shikang;Xie Yibin(Department of Pancreatic and Gastric Surgery,National Cancer Center,National Clinical Research Center for Cancer,Cancer Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100021,China;Department of Oncology,The First Affiliated Hospital of Zhengzhou University,Zhengzhou 450000,Henan,China;State Key Laboratory of Molecular Oncology,National Cancer Center,National Clinical Research Center for Cancer,Cancer Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100021,China)

机构地区：[1]国家癌症中心,国家肿瘤临床医学研究中心,中国医学科学院北京协和医学院肿瘤医院胰胃外科,北京100021 [2]郑州大学第一附属医院肿瘤科,河南郑州450000 [3]国家癌症中心,国家肿瘤临床医学研究中心,中国医学科学院北京协和医学院肿瘤医院分子肿瘤学国家重点实验室,北京100021

出　　处：《中国医学前沿杂志（电子版）》2022年第11期59-66,共8页Chinese Journal of the Frontiers of Medical Science(Electronic Version)

摘　　要：胃肠间质瘤作为最常见的间叶源性肿瘤,临床病理通过免疫组化染色CD117、DOG1、CD34、Desmin、平滑肌肌动蛋白、S-100蛋白进行诊断。随着基因测序技术的发展,胃肠间质瘤的诊断进入分子时代。胃肠间质瘤患者80%以上存在Kit或PDGFRA基因突变,这2种基因有数个突变位点和多种突变类型。2种基因均未突变的肿瘤称为野生型胃肠间质瘤,此类肿瘤具有罕见的基因突变类型。Kit和PDGFRA基因均编码Ⅲ型受体酪氨酸激酶,其病理性突变使得激酶失去抑制而自动激活。异常激活的酪氨酸激酶进一步激活下游PI3K-AKT-m TOR和RAS-MEK-MAPK通路,使得细胞增殖不受控制,细胞凋亡受到抑制。目前针对胃肠间质瘤的病理性突变,临床上研发了数代酪氨酸激酶抑制剂,治疗上均取得一定的成效。但是,酪氨酸激酶抑制剂用药2~3年或者停药后,胃肠间质瘤患者常常容易出现复发的情况。难治性复发胃肠间质瘤已经成为目前临床工作中需要解决的问题。目前,免疫治疗在胃肠间质瘤的治疗中崭露头角,胃肠间质瘤作为一种需多学科综合治疗的肿瘤,其精准治疗正在越来越规范与完善。本文就胃肠间质瘤分子发病机制及精准治疗研究进展进行综述。As the most common mesenchymal tumors,gastrointestinal stromal tumors were diagnosed by immunohistochemical staining of CD117,DOG1,CD34,Desmin,smooth muscle actin and S-100 protein.With the development of gene sequencing technology,the diagnosis of gastrointestinal stromal tumors has entered the molecular field.More than 80% gastrointestinal stromal tumors patients have Kit or PDGFRA gene mutations,which have several mutation sites and multiple mutation types.Tumors without Kit or PDGFRA mutations are called wild-type gastrointestinal stromal tumors,which have rare gene mutations.Both Kit and PDGFRA genes encode type Ⅲ receptor tyrosine kinase,and its pathological mutation induces the kinase lose inhibition and automatically activate.The abnormally activated tyrosine kinase further activated the downstream PI3K-AKT-m TOR and RAS-MEK-MAPK pathways,resulting in uncontrolled cell proliferation and inhibition of apoptosis.At present,several generations of tyrosine kinase inhibitors have been developed clinically for the pathological mutation of gastrointestinal stromal tumors, which have achieved certain results in treatment.However,patients with gastrointestinal stromal tumors often suffer from relapse after 2 to 3 years or withdrawal of tyrosine kinase inhibitors.Refractory recurrent gastrointestinal stromal tumor has become a problem to be solved in clinical.At present,immunotherapy is emerging in the treatment of gastrointestinal stromal tumors.As a tumor requiring multidisciplinary comprehensive treatment,the precise treatment of gastrointestinal stromal tumors is becoming more and more standardized and perfect.This article reviewed the molecular pathogenesis and precise treatment of gastrointestinal stromal tumors.

关 键 词：胃肠间质瘤 发病机制 靶向治疗 精准治疗 

分 类 号：R735[医药卫生—肿瘤]