Clinical implications of lactylation modification in digestive system tumors (Review).

Abstract

Lactylation, a novel post-translational modification, has emerged as a critical mechanistic link between metabolic reprogramming and epigenetic regulation in cancer. The present review aimed to synthesize emerging evidence on the role of lysine lactylation in the pathogenesis and progression of major digestive system malignancies, including esophageal, gastric, colorectal, hepatocellular and pancreatic cancer. The molecular mechanisms through which lactate-derived lactylation modifies histone and non-histone proteins are described, which thereby regulate key oncogenic processes such as metabolic adaptation, cancer stemness maintenance, epithelial-mesenchymal transition, immunosuppressive tumor microenvironment remodeling, angiogenesis, perineural invasion and therapeutic resistance. The translational potential of targeting the lactylation axis by inhibiting lactate production, blocking lactate transport or directly modulating lactylation-related enzymes are explored, and the development of lactylation-based prognostic models and their implications for innovative combination strategies to overcome treatment resistance are also highlighted. The present review highlights lactylation as a pivotal regulator in digestive oncology and a promising target for novel diagnostic and therapeutic strategies.