Oncometabolites are metabolites that, when accumulated, can promote cancer progression. For instance, mutations in IDH1 and IDH2 lead to the production of 2-hydroxyglutarate, which inhibits α-ketoglutarate-dependent dioxygenases, affecting DNA and histone methylation and altering gene expression. Similarly, accumulation of succinate and fumarate due to SDH and FH mutations inhibits prolyl hydroxylases, stabilizing hypoxia-inducible factors (HIFs) and promoting a hypoxic response, which supports tumorigenesis.
