PDF(Pubmed)
Abstract：
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.
摘要：
组蛋白脱乙酰酶（HDAC）在各种恶性肿瘤的病理生物学中起着关键的分子调节剂的作用，并作为治疗干预的可行靶标引起了人们的关注。已经开发了多种HDAC抑制剂(HDACis)来靶向HDAC。许多临床前研究最终证明了HDACis的抗肿瘤作用，无论是作为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，全面概述了目前靶向HDAC治疗的临床进展。此外，我们讨论了几个没有产生积极结果的临床试验，分析导致其缺乏预期治疗效果的因素。除了实验设计因素，毒理学副作用等问题，肿瘤异质性，意外的脱靶效应也导致了这些低于预期的结果。这些挑战自然成为HDACis应用的重大障碍。尽管面临这些挑战,我们相信,HDACi研究的进展和联合疗法的改进将为实体瘤治疗铺平道路或带来广阔而充满希望的未来.
