Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy characterized by late detection and poor prognosis. Recent research highlights the pivotal role of epigenetic alter- ations in driving PDAC development and progression. These changes, in conjunction with genetic mutations, contribute to the intricate molecular landscape of the disease. Specific modifications in DNA methylation, histone marks, and non-coding RNAs are emerging as robust predictors of disease progression and patient survival, offering the potential for more precise prognostic tools compared to conventional clinical staging. Moreover, the detection of epigenetic alterations in blood and other non-invasive samples holds promise for earlier diagnosis and improved manage- ment of PDAC. This review comprehensively summarises current epigenetic research in PDAC and identifies persisting challenges. These include the complex nature of epigenetic profiles, tumour hetero- geneity, limited access to early-stage samples, and the need for highly sensitive liquid biopsy technologies. Addressing these challenges requires the standardisation of methodologies, integra- tion of multi-omics data, and leveraging advanced computational tools such as machine learning and artificial intelligence. While resource-intensive, these efforts are essential for unravelling the functional consequences of epigenetic changes and translating this knowledge into clinical appli- cations. By overcoming these hurdles, epigenetic research has the potential to revolutionise the management of PDAC and improve patient outcomes.

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