The oncometabolite d‑2‑hydroxyglutarate induces angiogenic activity through the vascular endothelial growth factor receptor 2 signaling pathway.

The mutation of isocitrate dehydrogenase (IDH)1 (R132H) and IDH2 (R172K) and the induction of hypoxia in various solid tumors results in alterations in metabolic profiles, including the production of the d‑ or l‑forms of 2‑hydroxyglutarate (2HG) from α‑ketoglutarate in aerobic metabolism in the tricarboxylic acid (TCA) cycle. However, it is unclear whether the oncometabolite d‑2HG increases angiogenesis in endothelial cells. Therefore, in this study, we analyzed the levels of various metabolites, including d‑2HG, under hypoxic conditions and in IDH2R172K mutant breast cancer cells by mass spectrometry.