Histone deacetylases (HDACs) play an important role in regulating the expression of genes involved in tumorigenesis and tumor maintenance, and hence they have been considered as key targets in cancer therapy. As a novel category of antitumor agents, histone deacetylase inhibitors (HDACis) can induce cell cycle arrest, apoptosis, and differentiation in cancer cells, ultimately combating cancer. Although in the United States, the use of HDACis for the treatment of certain cancers has been approved, the therapeutic efficacy of HDACis as a single therapeutic agent in solid tumorshas been unsatisfactory and drug resistance may yet occur. To enhance therapeutic efficacy and limit drug resistance, numerous combination therapies involving HDACis in synergy with other antitumor therapies have been studied. In this review, we describe the classification of HDACs. Moreover, we summarize the antitumor mechanism of the HDACis for targeting key cellular processes of cancers (cell cycle, apoptosis, angiogenesis, DNA repair, and immune response). In addition, we outline the major developments of other antitumor therapies in combination with HDACis, including chemotherapy, radiotherapy, phototherapy, targeted therapy, and immunotherapy. Finally, we discuss the current state and challenges of HDACis-drugs combinations in future clinical studies, with the aim of optimizing the antitumor effect of such combinations.

组蛋白去乙酰化酶 (HDAC) 在调节参与肿瘤发生和肿瘤维持的基因表达方面发挥重要作用，因此它们被认为是癌症治疗的关键靶点。作为一类新型抗肿瘤药物，组蛋白去乙酰化酶抑制剂 (HDACis) 可以诱导癌细胞的细胞周期停滞、凋亡和分化，最终对抗癌症。虽然在美国已经批准使用HDACis治疗某些癌症，但HDACis作为单一治疗药物治疗实体瘤的疗效一直不尽如人意，还可能出现耐药性。为了提高疗效和限制耐药性，已经研究了许多涉及 HDACis 与其他抗肿瘤疗法协同作用的联合疗法。在这篇评论中，我们描述了 HDAC 的分类。此外，我们总结了 HDACis 针对癌症关键细胞过程（细胞周期、细胞凋亡、血管生成、DNA 修复和免疫反应）的抗肿瘤机制。此外，我们概述了其他抗肿瘤疗法联合 HDACis 的主要进展，包括化学疗法、放射疗法、光疗法、靶向疗法和免疫疗法。最后，我们讨论了 HDACis-药物组合在未来临床研究中的现状和挑战，目的是优化此类组合的抗肿瘤作用。我们概述了与 HDACis 联合使用的其他抗肿瘤疗法的主要进展，包括化学疗法、放射疗法、光疗法、靶向疗法和免疫疗法。最后，我们讨论了 HDACis-药物组合在未来临床研究中的现状和挑战，目的是优化此类组合的抗肿瘤作用。我们概述了与 HDACis 联合使用的其他抗肿瘤疗法的主要进展，包括化学疗法、放射疗法、光疗法、靶向疗法和免疫疗法。最后，我们讨论了 HDACis-药物组合在未来临床研究中的现状和挑战，目的是优化此类组合的抗肿瘤作用。