In addition to decreased α-ketoglutarate levels, Isaacs et al. revealed that fumarate, the levels of which are elevated as a result of a fumarate hydroxylase deficiency in cancer cells, also increases the expression levels of HIF-1α through inhibition of the activity of PDHs by directly competing with its co-factor, α-ketoglutarate [30]. The gene discussed is HIF1A; the disease is cancer.