Advances in pancreatic cancer epigenetics: From the mechanism to the clinic

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.

Keywords: Pancreatic cancer; Epigenetics; Diagnosis; Treatment; Prognosis

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.