HIF1A and chondrosarcoma: HIF-1α activates pyruvate dehydrogenase kinase, which inactivates pyruvate dehydrogenase, thereby inhibiting the influx of pyruvate into the TCA cycle.47 In this context, TCA cycle anaplerosis is required for the synthesis of fatty acids, which is then primarily mediated via glutaminolysis.48 Therefore, the hypoxic microenvironment of chondrosarcomas potentially explains why chondrosarcomas depend on glutaminolysis irrespective of the presence or absence of an IDH1/2 mutation.