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Review
. 2022 Oct;19(6):1724-1732.
doi: 10.1007/s13311-022-01238-3. Epub 2022 Apr 27.

Targeting IDH-Mutant Glioma

Julie J Miller  1
Affiliations
Review

Targeting IDH-Mutant Glioma

Julie J Miller. Neurotherapeutics. 2022 Oct.

Abstract

Standard treatment for patients with IDH-mutant gliomas with radiation therapy and chemotherapy is non-curative and associated with long-term neurotoxicity. This has created intense interest in targeted therapeutic strategies that are specifically designed of IDH-mutant tumors. Much progress has been made in understanding the unique biology of IDH-mutant gliomas, and now various IDH-mutant-specific targeting strategies are in various phases of development. Here, we will review a range of IDH-mutant targeting treatments being explored, including direct IDH inhibitors, as well as strategies that take advantage of IDH-mutant-specific vulnerabilities.

Keywords: 2-Hydroxyglutarate; Astrocytoma; Glioma; IDH1; Metabolism; Oligodendroglioma.

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Figures

Fig. 1
Fig. 1
IDH-mutant enzymes produce D-2-hydroxyglutarate (2-HG), which alters metabolic programs and promotes gliomagenesis. Direct targets of D-2-HG are shown in black. Drugs that target these various processes are shown in red. Abbreviations: IDH, isocitrate dehydrogenase; αKG, alpha ketoglutarate; NAD, nicotinamide adenine dinucleotide; NAPRT1, nicotinate phosphoribosyltransferase 1; NAMPT, nicotinamide phosphoribosyltransferase; BCAT1, branched chain amino acid transaminase 1; BCAA, branched chain amino acid; HR, homologous recombination; PARP, poly (ADP-ribose) polymerase; PARG, poly (ADP-ribose) glycohydrolase; DHODH, dihydroorotate dehydrogenase; KDMs, histone lysine demethylases; TET 1/2, ten-eleven translocation methylcytosine dioxygenase
See this image and copyright information in PMC

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