异柠檬酸脱氢酶基因突变治疗的研究进展  

Research Progress of Isocitrate Dehydrogenase Gene Mutation Therapy

作　　者：林美佳 曾也婷 王心睿 黄雄飞[1,5] LIN Meijia;ZENG Yeting;WANG Xinrui;HUANG Xiongfei(Department of Pathology,School of Basic Medical Sciences,Fujian Medical University,Fuzhou 350004,China;National Health Commission Key Laboratory of Nonhuman Primate Fertility Regulation Technology Evaluation(Fujian Maternity and Child Health Hospital),Fuzhou 350013,China;Department of Pathology,The 900th Hospital of Joint Logistic Support Force,People’s Liberation Army,Fuzhou 35001,China;Medical Research Center,Fujian Maternity and Child Health Hospital,Affiliated Hospital of Fujian Medical University,Fuzhou 350001,China;Key Laboratory of Gastrointestinal Malignancy of Ministry of Education,Fujian Medical University,Fuzhou 350108,China)

机构地区：[1]福建医科大学基础医学院病理学系,福州350004 [2]国家卫生健康委员会非人灵长类生育调节技术评价重点实验室(福建省妇幼保健院),福州350013 [3]中国人民解放军联勤保障部队第900医院病理科,福州350001 [4]福建医科大学附属医院福建省妇幼保健院医学研究中心,福州350001 [5]福建医科大学消化道恶性肿瘤教育部重点实验室,福州350108

出　　处：《协和医学杂志》2023年第2期346-352,共7页Medical Journal of Peking Union Medical College Hospital

基　　金：福建省自然科学基金(2022J01662)。

摘　　要：异柠檬酸脱氢酶(isocitrate dehydrogenase,IDH)作为三羧酸循环的关键酶,在细胞能量代谢中发挥重要作用。IDH基因突变可引起该酶的活性发生改变,导致大量肿瘤代谢物2-羟基戊二酸蓄积,从而引起严重的表观遗传调控紊乱和基因表达失调,促进肿瘤发生。近年来研究表明,IDH1和IDH2突变与胶质瘤、急性髓系白血病、肝内胆管癌等多种肿瘤的发生发展及其临床治疗具有密切关系。将IDH基因突变作为检测胶质瘤、急性髓系白血病、肝内胆管癌等肿瘤发生的分子标志物,以及靶向药物的开发位点具有重要意义。本文就IDH突变机制及其与多种肿瘤发生发展的关系,以及IDH突变治疗在基础研究和药物临床研究中的进展作一综述。Isocitrate dehydrogenase(IDH),a key enzyme in the tricarboxylic acid cycle,plays an important role in cellular energy metabolism.When the IDH gene is mutated,the enzyme activity is altered,resulting in an accumulation of a large amount of the tumor metabolite 2⁃hydroxyglutaric acid(2⁃HG),causing severe epigenetic deregulation and dysregulation of gene expression,and promoting tumorigenesis.Recent studies have shown that IDH1 and IDH2 mutations are closely related to the occurrence and development of a variety of tumors such as glioma,acute myeloid leukemia(AML)and intrahepatic cholangiocarcinoma(iCCA)as well as their clinical treatment.It is of great significance to use IDH gene mutations as molecular indicators for detecting glioma,AML and iCCA tumorigenesis,and developing targeted drugs.This review is focused on the mechanism of IDH mutation,the relationship between mutant IDH and the development of multiple tumors,and the progress of treatment of IDH mutation in basic research and drug clinical trials.

关 键 词：异柠檬酸脱氢酶突变 2-羟基戊二酸 化疗 免疫治疗 靶向治疗 

分 类 号：R-1[医药卫生] R730.5