REVIEW article
Front. Pharmacol.
Sec. Pharmacology of Anti-Cancer Drugs
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1589455
Targeting Super-Enhancers in Liver Cancer: From Pathogenic Mechanisms to Clinical Applications
Provisionally accepted- 1Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Qingdao University, Qingdao, China
- 2Department of Thoracic Surgery, Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, China
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Liver cancer, especially primary liver cancer (PLC), stands as the third leading cause of cancer-related mortality globally, posing a significant threat to human health. Super-enhancers (SEs), clusters of enhancer elements with high histone modifications and transcriptional activity levels, play crucial roles in diverse biological processes and are closely associated with the pathogenesis of various diseases, including liver cancer.This review first delves into the pathogenic mechanisms of super -enhancers in liver cancer. SEs can drive the aberrant expression of oncogenes in liver cancer. Through interactions with transcription factors and chromatin-modifying enzymes, SEs can reshape the chromatin architecture, facilitating the access of transcriptional machinery to oncogene promoters and resulting in their overexpression.Additionally, abnormal activation of signaling pathways in liver cancer can also regulate the formation and activity of SEs, creating a positive -feedback loop that fuels tumor development.We further explore how targeting SEs may translate into clinical applications for liver cancer. Therapeutic strategies, such as using small inhibitors that disrupt the function of key components in SE-mediated transcriptional complexes, have shown promise in preclinical studies. These inhibitors can specifically block the activity of SEs, leading to the down-regulation of oncogene expression and subsequent suppression of tumor cell growth. In addition, gene-editing technologies provide new tools for precisely modulating superenhancer activity in liver cancer cells. By deleting or modifying specific enhancer elements within SEs, the expression of oncogenes can be effectively controlled.In conclusion, understanding the pathogenic mechanisms of SEs in liver cancer and their clinical applications offers a new perspective on the diagnosis, treatment, and prognosis of liver cancer. However, more in-depth research is required to fully realize the potential of super-enhancer-targeted therapy in clinical settings in order to provide more effective treatment options for liver cancer patients.
Keywords: liver cancer, super-enhancer, Transcriptional Regulation Epigenetic modifications, therapeutic targets, clinical applications
Received: 07 Mar 2025; Accepted: 03 Jun 2025.
Copyright: © 2025 Li, Yao, Sun, Cao and Wang. 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:
Jingyu Cao, Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Qingdao University, Qingdao, China
Zusen Wang, Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Qingdao University, Qingdao, China
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.