IDH2 Mediated Metabolic Reprogramming and Targeted Drug Development
LIU Qiao, LUO Bingling, ZENG Peiting, QIAO Shuang, LI Jiangjiang, HUANG Peng*
IDH2 (isocitrate dehydrogenase 2) is a key enzyme that catalyzes the conversion between isocitrate and α-KG (α-ketoglutarate) in the TCA (tricarboxylic acid) cycle, which plays an important role in the tumor metabolic reprogramming. The IDHs family consists of IDH1, IDH2, and IDH3, which differ in their subcellular localizations and functions. Mutations and aberrant expression of IDH2 are commonly observed in various tumorigenic processes. The complexity of cancer metabolism and the diverse functional roles of metabolites present major challenges in targeting metabolic pathways for cancer therapy. This article focuses on metabolic abnormalities in cancer, especially the metabolic changes mediated by elevated expression of wild-type IDH2, and reviews the latest advancements in the development of IDH2-targeting therapeutics.
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