REVIEW article
Front. Epigenet. Epigenom.
Sec. Chromatin Epigenomics
This article is part of the Research TopicTranslational Epigenetics in Medicine: From Biomarker Discovery to Clinical ApplicationView all 4 articles
Epigenetic Dysregulation in Pancreatic Cancer: Emerging Biomarkers and Clinical Applications
Provisionally accepted
- 1Integrative Program for Biological and Genome Sciences, University of North Carolina at Chapel Hill, Chapel Hill, United States
- 2Division of Oral and Craniofacial Health Sciences, Adams School of Denistry, University of North Carolina at Chapel Hill, Chapel Hill, United States
- 3Department of Biotechnology, School of Bioengineering and Biosciences, Lovely Professional University, Jalandhar, India
- 4Department of Oncology Science, University of Oklahoma Health Sciences Center, Oklahoma City, United States
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Pancreatic cancer, in particular pancreatic ductal adenocarcinoma (PDAC), is one of the most lethal malignancies with delayed diagnosis, aggressive nature, and profound therapeutic resistance. Recent research has emphasized epigenetic dysregulation not as a bystander but as a driving force in pancreatic tumorigenesis, progression, metastasis, and immune evasion. This review presents a detailed analysis of the multifaceted functions of epigenetic mechanisms like DNA methylation, histone modifications, and non-coding RNAs in shaping the pancreatic cancer epigenome. We discuss how these alterations fuel tumor heterogeneity, modulate the tumor microenvironment, and interact with key oncogenic mutations like KRAS and TP53. Further, we discuss the potential of epigenetic alterations as diagnostic, prognostic, and predictive biomarkers with an emphasis on their application in liquid biopsies. Finally, we evaluate current and prospective epigenetic therapies, their cooperation with chemotherapy and immunotherapy, and the prospects of new approaches such as CRISPR-based epigenome editing and personalized epigenetic profiling. Together, these findings point to the epigenome as a powerful window of opportunity for understanding, diagnosing, and eventually targeting pancreatic cancer.
Keywords: Pancreatic ductal adenocarcinoma (PDAC), DNA methylation biomarkers, liquid biopsy, Epigenetic therapies, clinical translation, non-coding RNAs, miRNA biomarkers, lncRNA biomarkers
Received: 11 Oct 2025; Accepted: 17 Nov 2025.
Copyright: © 2025 Sultana, SOLOMON, Wani and Shukla. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Hina Sultana, sultanah@email.unc.edu
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