Molecular mechanisms and therapeutic strategies: DNA methylation in pancreatic cancer.

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.