关键词: 2-hydroxyglutarate cancer stem cells chemotherapy differentiation enasidenib isocitrate dehydrogenase ivosidenib targeted therapy therapy responses

Mesh : Antineoplastic Agents / pharmacology Cell Differentiation / drug effects Enzyme Inhibitors / pharmacology Humans Isocitrate Dehydrogenase / antagonists & inhibitors genetics metabolism Leukemia, Myeloid, Acute / drug therapy metabolism pathology Mutation Neoplastic Stem Cells / drug effects metabolism

来  源:   DOI:10.1369/00221554211062499

Abstract:
Isocitrate dehydrogenase 1 and 2 (IDH1/2) are enzymes recurrently mutated in various types of cancer, including glioma, cholangiocarcinoma, chondrosarcoma, and acute myeloid leukemia. Mutant IDH1/2 induce a block in differentiation and thereby contribute to the stemness and oncogenesis of their cells of origin. Recently, small-molecule inhibitors of mutant IDH1/2 have been Food and Drug Administration-approved for the treatment of IDH1/2-mutated acute myeloid leukemia. These inhibitors decrease the stemness of the targeted IDH1/2-mutated cancer cells and induce their differentiation to more mature cells. In this review, we elucidate the mechanisms by which mutant IDH1/2 induce a block in differentiation and the biological and clinical effects of the release into differentiation by mutant-IDH1/2 inhibitors. (J Histochem Cytochem 70:83-97, 2022).
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