Targeting Lactate Metabolism in Cancer Therapy: The Mechanism of Lactylation Modification and Prospects of Therapeutic Strategies

Tumor cells preferentially engage in aerobic glycolysis (the Warburg effect) despite normoxic conditions, manifesting in pathological glucose avidity and excessive lactate accu-mulation relative to adjacent normal tissues. Beyond serving as a glycolytic endpoint, lactate acts as a versatile oncometabolite. It epigenetically reinforces multidrug resistance by remod-eling the extracellular microenvironment and driving transcriptional reprogramming via intra-cellular lactylation. Mechanistic studies reveal that lactate-mediated chemoresistance arises from stabilization of DNA repair machineries and metabolic adaptation pathways. This review synthesizes current understanding of lactate/lactylation-mediated therapeutic resistance mech-anisms across solid tumors, while proposing actionable targets within lactate metabolic cir-cuitry. Pharmacological disruption of lactate homeostasis coupled with lactylation modulation may reverse tumor adaptive resilience and resensitize refractory cancers to conventional ther-apeutics.