Xiao S, Xu XZ, Liao M, Song DD, Tang JF, Zhou CF. Potential risks of histone deacetylase inhibitors in cancer therapeutics and feasible combination therapeutic strategies. World J Clin Oncol 2025; 16(8): 108768 [DOI: 10.5306/wjco.v16.i8.108768]
Corresponding Author of This Article
Ce-Fan Zhou, PhD, Professor, School of Life and Health Sciences, Institute of Biomedical Research, National "111" Center for Cellular Regulation and Molecular Pharmaceutics, Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei University of Technology, No. 28 Nanli Road, Wuhan 430068, Hubei Province, China. cefan@hbut.edu.cn
Research Domain of This Article
Medicine, Research & Experimental
Article-Type of This Article
Editorial
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/
Shuai Xiao, Xiao-Zhen Xu, Meng Liao, Dan-Dan Song, Jing-Feng Tang, Ce-Fan Zhou, School of Life and Health Sciences, Institute of Biomedical Research, National "111" Center for Cellular Regulation and Molecular Pharmaceutics, Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei University of Technology, Wuhan 430068, Hubei Province, China
Co-corresponding authors: Jing-Feng Tang and Ce-Fan Zhou.
Author contributions: Tang JF and Zhou CF contribute equally to this study as co-corresponding authors; Xiao S prepared the original draft; Zhou CF and Tang JF contributed to the conceptualization, writing, review, and editing of the manuscript; Xu XZ, Liao M, and Song DD collaboratively drafted the manuscript; all authors have reviewed and approved the final version of the manuscript.
Supported by National Natural Science Foundation of China, No. 32270768, No. 82273970, No. 32070726 and No. 82370715; Hubei Natural Science Foundation of China, No. 2024AFB218; National Key R&D Program of China, No. 2023YFC2507904; and Doctoral Start-up Foundation of Hubei University of Technology, No. XJ2022003901.
Conflict-of-interest statement: The authors declare that there are 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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Ce-Fan Zhou, PhD, Professor, School of Life and Health Sciences, Institute of Biomedical Research, National "111" Center for Cellular Regulation and Molecular Pharmaceutics, Key Laboratory of Fermentation Engineering (Ministry of Education), Hubei University of Technology, No. 28 Nanli Road, Wuhan 430068, Hubei Province, China. cefan@hbut.edu.cn
Received: April 23, 2025 Revised: May 21, 2025 Accepted: July 10, 2025 Published online: August 24, 2025 Processing time: 119 Days and 18.4 Hours
Abstract
Histone deacetylase inhibitors (HDACis), such as trichostatin A (TSA), have been recognized as promising anti-cancer agents due to their capacity to restore epigenetic regulation and reactivate tumor suppressor genes. However, emerging evidence indicates that unintended pro-metastatic effects may offset the therapeutic benefits of HDACis. Chen et al elucidate this paradox, demonstrating that TSA-induced hyperacetylation activates the BRD4/c-Myc/ER-stress axis, thereby promoting epithelial-mesenchymal transition and metastasis in esophageal squamous cell carcinoma (ESCC). Furthermore, they clarify the clinical significance of histone acetylation in the prognostic evaluation of ESCC. Their findings underscore the complexity of epigenetic therapies and highlight the necessity of reevaluating the associated risks and combinatorial therapeutic strategies with HDACi-based treatments. Here, we summarize the potential risks of HDACis therapy and discuss feasible combination therapeutic strategies.
Core Tip: Histone deacetylase inhibitors (HDACis) have been extensively researched for their potential anticancer effects. However, in addition to their role in inhibiting tumor growth, it has also surprisingly facilitated the metastasis of esophageal squamous cell carcinoma. Clinical studies indicate that the effectiveness of HDACis in treating solid tumors often falls short of expectations, and these inhibitors may inherently carry certain risks. In this article, we examine the potential dangers associated with the clinical use of HDACis, including severe adverse effects, off-target toxicities, multidrug resistance, and limited efficiency in solid tumors. Furthermore, future research should focus on combination therapies, the development of selective or dual-target inhibitors to mitigate the adverse effects of HDACis treatments.
