Zhang Ying, Wang Haotian, Zhan Zhumei, Gan Lin, Bai Out
Department of Hematology, The First Hospital of Jilin University, Changchun, China.
Department of Hematology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.
Front Immunol. 2025 Apr 7;16:1529239. doi: 10.3389/fimmu.2025.1529239. eCollection 2025.
Histone deacetylases (HDACs) are a class of epigenetic regulators that play pivotal roles in key biological processes such as cell proliferation, differentiation, metabolism, and immune regulation. Based on this, HDAC inhibitors (HDACis), as novel epigenetic-targeted therapeutic agents, have demonstrated significant antitumor potential by inducing cell cycle arrest, activating apoptosis, and modulating the immune microenvironment. Current research is focused on developing highly selective HDAC isoform inhibitors and combination therapy strategies tailored to molecular subtypes, aiming to overcome off-target effects and resistance issues associated with traditional broad-spectrum inhibitors. This review systematically elaborates on the multidimensional regulatory networks of HDACs in tumor malignancy and assesses the clinical translation progress of next-generation HDACis and their prospects in precision medicine, providing a theoretical framework and strategic reference for the development of epigenetic-targeted antitumor drugs.
组蛋白去乙酰化酶（HDACs）是一类表观遗传调节因子，在细胞增殖、分化、代谢和免疫调节等关键生物学过程中发挥着关键作用。基于此，HDAC抑制剂（HDACis）作为新型的表观遗传靶向治疗药物，通过诱导细胞周期停滞、激活细胞凋亡和调节免疫微环境，已显示出显著的抗肿瘤潜力。当前的研究集中在开发高度选择性的HDAC亚型抑制剂以及针对分子亚型的联合治疗策略，旨在克服与传统广谱抑制剂相关的脱靶效应和耐药问题。本综述系统地阐述了HDACs在肿瘤恶性进展中的多维调控网络，并评估了下一代HDACis的临床转化进展及其在精准医学中的前景，为表观遗传靶向抗肿瘤药物的开发提供了理论框架和战略参考。
