Histone Lactylation in Cancer: Linking Hypoxia-Driven Metabolism to Epigenetic Regulation

Abstract

Solid tumors are frequently characterized by hypoxia, which drives metabolic reprogramming toward glycolysis and increased lactate production. Beyond its role as a metabolic end product, lactate can influence gene regulation through histone lactylation, a recently identified post-translational modification linking cellular metabolism with epigenetic regulation. In cancer, hypoxia-associated lactate accumulation and histone lactylation have been implicated in tumor proliferation, invasion, epithelial–mesenchymal transition, immune modulation, and therapeutic resistance. This review summarizes current knowledge of the relationship between hypoxia, lactate metabolism, and histone lactylation, focusing on the molecular mechanisms regulating this modification and its potential role in cancer progression. We also discuss current methodological challenges and the potential of the lactate–histone lactylation axis as a target for future diagnostic and therapeutic strategies in oncology.