以组蛋白去乙酰化酶为靶点治疗实体瘤的进展

IF 29.5 1区 医学 Q1 HEMATOLOGY
Mu-Qi Shi, Ying Xu, Xin Fu, De-Si Pan, Xian-Ping Lu, Yi Xiao, Yi-Zhou Jiang
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引用次数: 0

摘要

组蛋白去乙酰化酶(HDAC)是各种恶性肿瘤病理生物学过程中的关键分子调控因子,并作为一种可行的治疗干预靶点而备受关注。目前已开发出多种针对 HDAC 的 HDAC 抑制剂(HDACis)。许多临床前研究已经确证了 HDACis 的抗肿瘤作用,无论是作为单一疗法还是联合疗法。在此基础上,研究人员开展了各种临床研究,以评估选择性和泛 HDACis 在临床中的潜力。在我们的工作中,我们广泛总结和整理了当前的临床试验,全面概述了当前针对 HDAC 治疗的临床进展。此外,我们还对几项未取得积极成果的临床试验进行了讨论,分析了导致其缺乏预期疗效的因素。除了实验设计因素外,毒副作用、肿瘤异质性和意外的脱靶效应等问题也是导致这些结果不如预期的原因。这些挑战自然成为 HDACis 应用的重大障碍。尽管存在这些挑战,但我们相信,HDACi 研究的进展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。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Advances in targeting histone deacetylase for treatment of solid tumors
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.
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来源期刊
CiteScore
48.10
自引率
2.10%
发文量
169
审稿时长
6-12 weeks
期刊介绍: The Journal of Hematology & Oncology, an open-access journal, publishes high-quality research covering all aspects of hematology and oncology, including reviews and research highlights on "hot topics" by leading experts. Given the close relationship and rapid evolution of hematology and oncology, the journal aims to meet the demand for a dedicated platform for publishing discoveries from both fields. It serves as an international platform for sharing laboratory and clinical findings among laboratory scientists, physician scientists, hematologists, and oncologists in an open-access format. With a rapid turnaround time from submission to publication, the journal facilitates real-time sharing of knowledge and new successes.
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