D-2-Hydroxyglutarate in Glioma Biology
CELLS(2021)
Abstract
Isocitrate dehydrogenase (IDH) mutations are common genetic abnormalities in glioma, which result in the accumulation of an "oncometabolite", D-2-hydroxyglutarate (D-2-HG). Abnormally elevated D-2-HG levels result in a distinctive pattern in cancer biology, through competitively inhibiting alpha-ketoglutarate (alpha-KG)/Fe(II)-dependent dioxgenases (alpha-KGDDs). Recent studies have revealed that D-2-HG affects DNA/histone methylation, hypoxia signaling, DNA repair, and redox homeostasis, which impacts the oncogenesis of IDH-mutated cancers. In this review, we will discuss the current understanding of D-2-HG in cancer biology, as well as the emerging opportunities in therapeutics in IDH-mutated glioma.
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Key words
glioma,oncometabolites,IDH1,2(mut),D-2-HG,epigenetic,DDR,redox
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