Oncometabolites in Cancer Metabolism: Mechanistic Insights and Biomarker Potential‐ A Narrative Review

Abstract

Cancer cells undergo adaptation in hostile tumor microenvironments and go through extensive metabolic reprogramming for flourishing. Oncogenic transformation caused by mutations in some metabolic enzymes results in the generation of some metabolic intermediates called onco‐metabolites. A growing body of evidence highlights the role of oncometabolites such as 2‐hydroxyglutarate (2‐HG), fumarate, and succinate in driving oncogenesis through epigenetic remodeling, altered redox balance, and interrupted cellular signaling. These metabolites are usually accumulated due to mutation in major metabolic enzymes, including Isocitrate Dehydrogenase 1 and 2 (IDH1/2), Succinate Dehydrogenase (SDH), and Fumarate Hydratase (FH), and serve as competitive inhibitors of α‐ketoglutarate–dependent dioxygenases, thereby affecting DNA and histone demethylation. This review widely synthesizes the origin, biochemical functions, and oncogenic implications of oncometabolites, emphasizing their potential utility as diagnostic and prognostic biomarkers through liquid biopsy and metabolomic profiling.