Zhou JD, Shen HZ. Advances in pancreatic cancer epigenetics: From the mechanism to the clinic. World J Gastrointest Oncol 2025; 17(7): 106238 [DOI: 10.4251/wjgo.v17.i7.106238]
Corresponding Author of This Article
Hong-Zhang Shen, MD, PhD, Adjunct Associate Professor, Associate Chief Physician, Department of Gastroenterology, Hangzhou First People's Hospital, No. 256 Huansha Road, Shangcheng District, Hangzhou 310000, Zhejiang Province, China. shenhongzhang@zju.edu.cn
Research Domain of This Article
Oncology
Article-Type of This Article
Review
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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: http://creativecommons.org/licenses/by-nc/4.0/
World J Gastrointest Oncol. Jul 15, 2025; 17(7): 106238 Published online Jul 15, 2025. doi: 10.4251/wjgo.v17.i7.106238
Advances in pancreatic cancer epigenetics: From the mechanism to the clinic
Jia-Dan Zhou, Hong-Zhang Shen
Jia-Dan Zhou, Department of Gastroenterology, The Fourth School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou 310000, Zhejiang Province, China
Hong-Zhang Shen, Department of Gastroenterology, Hangzhou First People's Hospital, Hangzhou 310000, Zhejiang Province, China
Author contributions: Shen HZ conceptualized and designed the study, Shen HZ and Zhou JD conducted the literature review, and Zhou JD drafted the original manuscript; Shen HZ supervised the study, made critical revisions, and approved the final version. All authors prepared the draft and approved the submitted version.
Supported by National Natural Science Foundation of China, No. 82304628; and Natural Science Foundation of Zhejiang Province, No. LQ23H160047.
Conflict-of-interest statement: The authors declare that they have no competing interests.
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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Hong-Zhang Shen, MD, PhD, Adjunct Associate Professor, Associate Chief Physician, Department of Gastroenterology, Hangzhou First People's Hospital, No. 256 Huansha Road, Shangcheng District, Hangzhou 310000, Zhejiang Province, China. shenhongzhang@zju.edu.cn
Received: March 3, 2025 Revised: April 20, 2025 Accepted: June 3, 2025 Published online: July 15, 2025 Processing time: 135 Days and 22 Hours
Abstract
Pancreatic cancer (PC) is a highly malignant digestive system cancer that is difficult to diagnose early and is highly resistant to conventional treatments. Recent studies on epigenetics have provided new insights into the early diagnosis of PC and treatments including immunotherapy. Epigenetic changes can alter gene expression without altering the DNA sequence, involving mechanisms such as DNA methylation, histone modification, and the abnormal expression of noncoding RNAs. These mechanisms play crucial roles in the occurrence, development, and therapeutic response of tumors. This review summarizes progress in epigenetic research on PC and discusses the epigenetic characteristics, underlying mechanisms, early diagnosis, prognostic evaluation, treatment strategies, and future challenges for PC. Strategies targeting epigenetic changes may restore the expression of tumor suppressor genes and regulate the immune microenvironment and may be combined with immune checkpoint inhibitors as a new approach for the precise treatment of PC. However, there are challenges associated with the clinical application of epigenetic therapy, such as the development of resistance and adverse side effects, and challenges in target selection, so new epigenetic drugs and combination treatment strategies are needed. With the development of precision medicine, the integration of epigenetics and clinical medicine research has yielded broadly applicable findings. Interdisciplinary cooperation and advancements in clinical trials will further promote the application of epigenetics in PC research, providing more effective treatment options for patients. In the future, the combined application of epigenetic therapy and immunotherapy, the design of personalized treatment plans, and the development of technologies such as liquid biopsy will likely change the treatment landscape of PC.
Core Tip: Pancreatic cancer (PC) is a highly malignant cancer that is difficult to diagnose early and is resistant to conventional treatments. Epigenetic modifications, including DNA methylation, histone modification, and noncoding RNA expression, regulate gene expression without altering DNA sequences and play key roles in tumor development and treatment responses. This review discusses the epigenetic mechanisms, early diagnosis, prognosis, and treatment strategies for PC. Epigenetics, combined with immunotherapies, offers new treatment possibilities, but challenges remain, including resistance and side effects. The integration of epigenetics and precision medicine holds great potential for improving PC treatment and outcomes.
