HIF1A and central nervous system cancer: Initial studies in glioma cell lines reported the expected 2-HG inhibitory effects on PHDs and consequent elevated HIF-1α levels; overexpression of mutant-IDH, down-regulation of wild-type IDH1 or exogenous 2-HG supplementation up-regulated HIF-1α, whilst concurrent exogenous supplementation of α-KG with 2-HG reversed the 2-HG-induced increase in HIF-1α [35,75].