Neuro-Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, 20892, USA.
Br J Cancer. 2020 May;122(11):1580-1589. doi: 10.1038/s41416-020-0814-x. Epub 2020 Apr 15.
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.
异柠檬酸脱氢酶（IDH）酶催化异柠檬酸的氧化脱羧，因此在三羧酸循环和细胞内稳态中发挥关键作用。过去十年中癌症遗传学的重大进展揭示了编码 IDH 的基因在多种人类恶性肿瘤中经常发生突变，包括神经胶质瘤、急性髓系白血病、胆管癌、软骨肉瘤和甲状腺癌。一系列开创性的研究进一步阐明了 IDH 突变的生物学影响，并揭示了 IDH 突变体在致癌作用中的潜在作用。值得注意的是，IDH 突变体的新表型活性在癌症代谢、表观遗传改变和治疗耐药性方面建立了独特的模式。已经开发了新的分子靶向方法来提高针对 IDH 突变癌症的治疗效果。本文概述了 IDH 突变的人类恶性肿瘤的最新发现，重点讨论了神经胶质瘤，讨论了转化研究中的独特生物学特征和进展。
