Targeting Cancer Metabolism

    Tumor cells metabolize glucose, lactate, pyruvate, hydroxybutyrate, acetate, glutamine, arginine, and fatty acids at a much higher rates than nontumor tissue.
    These intermediary metabolites are released by catabolic cells, taken up by tumor cells and used to replenish TCA-cycle intermediates and to fuel oxidative phosphorylation (reverse Warburg effect).
    Enasidenib (formerly AG-221) is a first-in-class inhibitor of mutated isocitrate dehydrogenase 2 (IDH2) and is now FDA-approved to treat acute myeloid leukemia. The IDH enzyme normally metabolizes isocitrate into α-ketoglutarate. When mutated, it also convert α-ketoglutarate into 2-hydroxyglutarate, an oncometabolite that causes cell rentiation defects by impairing histone demethylation.
    Other topics in Molecular Targets and Pathways