IDH mutation in glioma: molecular mechanisms and potential therapeutic targets

被引：433

作者：

Han, Sue ^{[1
]}

Liu, Yang ^{[1
]}

Cai, Sabrina J. ^{[1
]}

Qian, Mingyu ^{[1
]}

Ding, Jianyi ^{[1
]}

Larion, Mioara ^{[1
]}

Gilbert, Mark R. ^{[1
]}

Yang, Chunzhang ^{[1
]}

机构：

[1] NCI, Neurooncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA

来源：

BRITISH JOURNAL OF CANCER | 2020年 / 122卷 / 11期

关键词：

ISOCITRATE DEHYDROGENASE 1; ACUTE MYELOID-LEUKEMIA; INDUCED OXIDATIVE STRESS; DNA-REPAIR ENZYMES; MUTANT IDH1; ONCOMETABOLITE; 2-HYDROXYGLUTARATE; HOMOLOGOUS RECOMBINATION; PROMOTES DIFFERENTIATION; LACTATE-DEHYDROGENASE; HISTONE DEMETHYLATION;

D O I：

10.1038/s41416-020-0814-x

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Isocitrate dehydrogenase (IDH) enzymes catalyse the oxidative decarboxylation of isocitrate and therefore play key roles in the Krebs cycle and cellular homoeostasis. Major advances in cancer genetics over the past decade have revealed that the genes encoding IDHs are frequently mutated in a variety of human malignancies, including gliomas, acute myeloid leukaemia, cholangiocarcinoma, chondrosarcoma and thyroid carcinoma. A series of seminal studies further elucidated the biological impact of the IDH mutation and uncovered the potential role of IDH mutants in oncogenesis. Notably, the neomorphic activity of the IDH mutants establishes distinctive patterns in cancer metabolism, epigenetic shift and therapy resistance. Novel molecular targeting approaches have been developed to improve the efficacy of therapeutics against IDH-mutated cancers. Here we provide an overview of the latest findings in IDH-mutated human malignancies, with a focus on glioma, discussing unique biological signatures and proceedings in translational research.

引用

页码：1580 / 1589

页数：10

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