Histone deacetylase (HDAC) serves as a critical molecular regulator in the pathobiology of various malignancies and have garnered attention as a viable target for therapeutic intervention. A variety of HDAC inhibitors (HDACis) have been developed to target HDACs. Many preclinical studies have conclusively demonstrated the antitumor effects of HDACis, whether used as monotherapy or in combination treatments. On this basis, researchers have conducted various clinical studies to evaluate the potential of selective and pan-HDACis in clinical settings. In our work, we extensively summarized and organized current clinical trials, providing a comprehensive overview of the current clinical advancements in targeting HDAC therapy. Furthermore, we engaged in discussions about several clinical trials that did not yield positive outcomes, analyzing the factors that led to their lack of anticipated therapeutic effectiveness. Apart from the experimental design factors, issues such as toxicological side effects, tumor heterogeneity, and unexpected off-target effects also contributed to these less-than-expected results. These challenges have naturally become significant barriers to the application of HDACis. Despite these challenges, we believe that advancements in HDACi research and improvements in combination therapies will pave the way or lead to a broad and hopeful future in the treatment of solid tumors.

中文翻译：

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靶向组蛋白脱乙酰酶治疗实体瘤的研究进展


组蛋白脱乙酰酶 （HDAC） 是各种恶性肿瘤病理学中的关键分子调节因子，并作为治疗干预的可行靶点而受到关注。已经开发了多种靶向 HDAC 的 HDAC 抑制剂 （HDACis）。许多临床前研究已最终证明 HDACis 的抗肿瘤作用，无论是用作单一疗法还是联合治疗。在此基础上，研究人员进行了各种临床研究，以评估选择性和泛 HDACis 在临床环境中的潜力。在我们的工作中，我们广泛总结和组织了当前的临床试验，全面概述了当前靶向 HDAC 治疗的临床进展。此外，我们参与了几项未产生积极结果的临床试验的讨论，分析了导致它们缺乏预期治疗效果的因素。除了实验设计因素外，毒理学副作用、肿瘤异质性和意外脱靶效应等问题也导致了这些低于预期的结果。这些挑战自然而然地成为 HDACis 应用的重大障碍。尽管存在这些挑战，但我们相信 HDACi 研究的进步和联合疗法的改进将为实体瘤的治疗铺平道路或带来广阔而充满希望的未来。