Isocitrate dehydrogenase 1 and 2 (IDH1/2) are key enzymes in cellular metabolism, epigenetic regulation, redox states, and DNA repair. IDH1/2 mutations are causal in the development and/or progression of various types of cancer due to supraphysiological production of D-2-hydroxyglutarate. In various tumor types, IDH1/2-mutated cancers predict for improved responses to treatment with irradiation or chemotherapy. The present review discusses the molecular basis of the sensitivity of IDH1/2-mutated cancers with respect to the function of mutated IDH1/2 in cellular processes and their interactions with novel IDH1/2-mutant inhibitors. Finally, lessons learned from IDH1/2 mutations for future clinical applications in IDH1/2 wild-type cancers are discussed.

中文翻译：

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野生型和突变的 IDH1/2 酶和治疗反应。

异柠檬酸脱氢酶 1 和 2 (IDH1/2) 是细胞代谢、表观遗传调控、氧化还原状态和 DNA 修复的关键酶。由于 D-2-羟基戊二酸的超生理产生，IDH1/2 突变是各种癌症发生和/或进展的原因。在各种肿瘤类型中，IDH1/2 突变的癌症预测对放射或化学治疗的反应会有所改善。本综述讨论了 IDH1/2 突变癌症对突变 IDH1/2 在细胞过程中的功能及其与新型 IDH1/2 突变抑制剂相互作用的敏感性的分子基础。最后，讨论了从 IDH1/2 突变中吸取的教训，以供未来在 IDH1/2 野生型癌症中的临床应用。