Lactylation,an emerging epigenetic modification,has recently been found to have significant ef-fects on the metabolic reprogramming of gastrointestinal tumors and the regulation of the tumor microenvironment.Lactate mediates lactylation modification via its metabolic intermediate lactyl-CoA.This novel post-translational mod-ification mechanism regulates the conformation and functionality of both histones and non-histone proteins through the specific conjugation of lactate moieties to lysine residues,thereby demonstrating critical associations with gene expression regulation,tumor progression(including growth,invasion,metastasis),immune evasion,and chemoresis-tance.This review systematically summarizes the molecular mechanisms of lactate metabolism and lactylation,as well as their biological functions and clinical significance in gastrointestinal cancers such as gastric cancer,colorectal can-cer,and liver cancer.The article also discusses therapeutic strategies targeting lactate and lactylation,including inhibi-tion of lactate metabolism pathways,intervention in lactylation modifications,and novel directions for combination therapy.Despite the challenges in studying the molecular mechanisms of lactylation and developing targeted drugs,research on lactylation as a potential therapeutic target shows great promise and provides new insights into the precise diagnosis,treatment,and overcoming chemotherapy resistance in gastrointestinal tumors.
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