Université de Nantes, CRCINA, INSERM, CNRS, F-44000, Nantes, France.
Institut de Cancérologie de l'Ouest, Saint-Herblain, France.
Oncogene. 2022 Jan;41(5):613-621. doi: 10.1038/s41388-021-02056-1. Epub 2021 Nov 11.
Brain tumors actively reprogram their cellular metabolism to survive and proliferate, thus offering potential therapeutic opportunities. Over the past decade, extensive research has been done on mutant IDH enzymes as markers of good prognosis in glioblastoma, a highly aggressive brain tumor in adults with dismal prognosis. Yet, 95% of glioblastoma are IDH wild-type. Here, we review current knowledge about IDH wild-type enzymes and their putative role in mechanisms driving tumor progression. After a brief overview on tumor metabolic adaptation, we present the diverse metabolic function of IDH enzymes and their roles in glioblastoma initiation, progression and response to treatments. Finally, we will discuss wild-type IDH targeting in primary glioblastoma.
脑肿瘤会积极重编程其细胞代谢以存活和增殖，从而提供潜在的治疗机会。在过去的十年中，人们对突变 IDH 酶作为胶质母细胞瘤（一种预后不良的成人高度侵袭性脑肿瘤）的预后良好标志物进行了广泛的研究。然而，95%的胶质母细胞瘤是 IDH 野生型。在这里，我们回顾了关于 IDH 野生型酶及其在驱动肿瘤进展的机制中潜在作用的现有知识。在简要概述肿瘤代谢适应后，我们介绍了 IDH 酶的多种代谢功能及其在胶质母细胞瘤发生、进展和对治疗的反应中的作用。最后，我们将讨论原发性胶质母细胞瘤中 IDH 野生型的靶向治疗。
