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World J Gastrointest Oncol. Sep 15, 2023; 15(9): 1505-1519
Published online Sep 15, 2023. doi: 10.4251/wjgo.v15.i9.1505
Deoxyribonucleic acid methylation driven aberrations in pancreatic cancer-related pathways
Akash Bararia, Amlan Das, Sangeeta Mitra, Sudeep Banerjee, Aniruddha Chatterjee, Nilabja Sikdar
Akash Bararia, Nilabja Sikdar, Human Genetics Unit, Indian Statistical Institute, Kolkata 700108, India
Amlan Das, Department of Biochemistry, Royal Global University, Assam 781035, India
Sangeeta Mitra, Department of Biochemistry and Biophysics, University of Kalyani, West Bengal 741235, India
Sudeep Banerjee, Department of Gastrointestinal Surgery, Tata Medical Center, Kolkata 700160, India
Aniruddha Chatterjee, Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin 9054, New Zealand
Aniruddha Chatterjee, School of Health Sciences and Technology, University of Petroleum and Energy Studies, Dehradun 248007, India
Author contributions: Bararia A, Das A, and Mitra S wrote the first draft of the paper and constructed the flow chart and tables; Chatterjee A, Banerjee S, and Sikdar N provided valuable input, suggestions, comments and guidance while writing the review manuscript and contributed to proofreading and editing; Sikdar N constructed, conceptualized, and edited the review manuscript.
Supported by the Department of Biotechnology, Government of India Grant Sanction, Ramalingaswami Re-entry Fellowship, No. RLS/BT/Re-entry/05/2012.
Conflict-of-interest statement: All the authors declare no conflicts of interest.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Nilabja Sikdar, PhD, Research Scientist, Doctor, Human Genetics Unit, Indian Statistical Institute, 203, B.T. Road, Kolkata 700108, India.
Received: April 18, 2023
Peer-review started: April 18, 2023
First decision: May 12, 2023
Revised: May 29, 2023
Accepted: August 1, 2023
Article in press: August 1, 2023
Published online: September 15, 2023

Pancreatic cancer (PanCa) presents a catastrophic disease with poor overall survival at advanced stages, with immediate requirement of new and effective treatment options. Besides genetic mutations, epigenetic dysregulation of signaling pathway-associated enriched genes are considered as novel therapeutic target. Mechanisms beneath the deoxyribonucleic acid methylation and its utility in developing of epi-drugs in PanCa are under trails. Combinations of epigenetic medicines with conventional cytotoxic treatments or targeted therapy are promising options to improving the dismal response and survival rate of PanCa patients. Recent studies have identified potentially valid pathways that support the prediction that future PanCa clinical trials will include vigorous testing of epigenomic therapies. Epigenetics thus promises to generate a significant amount of new knowledge of biological and medical importance. Our review could identify various components of epigenetic mechanisms known to be involved in the initiation and development of pancreatic ductal adenocarcinoma and related precancerous lesions, and novel pharmacological strategies that target these components could potentially lead to breakthroughs. We aim to highlight the possibilities that exist and the potential therapeutic interventions.

Keywords: Methylation driven pathways, Pancreatic cancer methylation markers, Signaling pathway targeted therapy, PanCa enriched methylated pathway, Pre-cancer methylated pathways

Core Tip: Given the limited commercial availability of targeted epi-drugs and pathway-based biomarkers, it is important to generalize them for appropriate treatment of pancreatic cancer and related precancerous lesions. We also highlighted the clinical use of these therapeutic targets based on methylation driven pathways. This review will successfully help readers address current issues and support cutting-edge development of targeted therapies using epigenetically regulated pathways.