O-GlcNAcylation Facilitates the Initiation and Progression of Digestive Tumors.

The escalating global burden of digestive system cancers, marked by high morbidity, mortality, and drug resistance, necessitates a more profound understanding of the mechanisms underlying tumorigenesis. Accumulating evidence underscores the pivotal role of O-GlcNAcylation-a dynamic posttranslational modification-mediated by O-GlcNAc transferase (OGT)-in promoting digestive system tumors. Elevated levels of O-GlcNAcylation are intricately associated with tumor progression, metastasis, immune evasion, and chemotherapy resistance. Targeting OGT or its downstream effectors represents a promising strategy to overcome drug resistance and enhance therapeutic efficacy. This review innovatively integrates the core perspective of the metabolism-immune-epigenetics regulatory axis. Based on comprehensive preclinical and clinical evidence, it systematically elaborates on the translational potential of modulating O-GlcNAcylation in precision oncology for digestive system tumors, while emphasizing the necessity for future in-depth mechanistic studies and clinical validation.