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

## TL;DR

This review explores how DNA methylation changes contribute to pancreatic cancer and how they might be used for early detection and treatment.

## Contribution

The paper highlights DNA methylation as a potential therapeutic target and biomarker in pancreatic cancer.

## Key findings

- Pancreatic cancer shows hypermethylation of tumor suppressor genes and hypomethylation at specific loci.
- Methylation-based biomarkers may aid in early detection and prognosis.
- DNA methyltransferase inhibitors show promise in preclinical and early clinical studies.

## Abstract

This narrative review examines DNA methylation dysregulation in pancreatic cancer, focusing on its mechanistic roles in tumorigenesis and applications in biomarkers and therapies.

We analyzed experimental and clinical studies on aberrant DNA methylation patterns, emphasizing their links to invasion, metastasis, therapy resistance, and immune modulation.

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.

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.

DNA methylation is a actionable regulatory layer in pancreatic cancer, but further mechanistic and clinical validation is needed for translational impact.