Abstract
OBJECTIVE: This narrative review examines DNA methylation dysregulation in pancreatic cancer, focusing on its mechanistic roles in tumorigenesis and applications in biomarkers and therapies. METHODS: We analyzed experimental and clinical studies on aberrant DNA methylation patterns, emphasizing their links to invasion, metastasis, therapy resistance, and immune modulation. RESULTS: Pancreatic cancer exhibits recurrent tumor suppressor gene hypermethylation and locus-specific hypomethylation, driving progression and resistance. Methylation-based biomarkers (tissue/cfDNA) show promise for early detection and prognostication, though evidence remains largely retrospective or preclinical. DISCUSSION: DNA methyltransferase inhibitors, alone or combined with immunotherapy/targeted agents, demonstrate preclinical and early clinical efficacy. Key challenges include mechanistic gaps, tumor heterogeneity, and assay standardization. CONCLUSION: DNA methylation is a actionable regulatory layer in pancreatic cancer, but further mechanistic and clinical validation is needed for translational impact.