Research progress and prospect of histone lactylation in digestive system tumors

Histone lactylation is a novel type of post-translational modification, where a lactate molecule covalently binds to the lysine residues of histones. This modification plays a key role in cellular metabolic reprogramming, particularly in digestive system tumorigenesis and progression. In recent years, the role of histone lactylation in various malignancies has been increasingly recognized, highlighting its broad impact on tumor biology and clinical potential. This article focused on the research progress of histone lactylation in digestive system cancers, specifically analyzing its mechanisms in major gastrointestinal cancers such as gastric cancer, liver cancer, and colon cancer. Studies have shown that lactylation modifies histone lysine residues directly, regulating tumor cell gene expression and chromatin conformation, thereby promoting tumor proliferation, invasion, and metastasis. Lactylation affects histone-DNA interactions, altering chromatin openness and enhancing the transcriptional activity of oncogenes. In addition, targeted therapies that modulate lactation levels or inhibit lactation-related enzymes, such as lactate dehydrogenase inhibitors, lactate production inhibitors, and specific histone lactonases, are effective in inhibiting tumorigenesis and progression and have demonstrated potential therapeutic efficacy in preclinical models. This article systematically summarized the mechanisms of histone lactylation in various types of gastrointestinal cancers, offering new research directions and theoretical support for targeted therapeutic strategies based on lactylation modification.