Department of Immunology, Centre of Biostructure Research, Medical University of Warsaw, Banacha 1A, F building, 02-097 Warsaw, Poland.
Front Biosci (Landmark Ed). 2011 Jan 1;16(1):340-59. doi: 10.2741/3691.
Histone deacetylases inhibitors (HDACi) have recently emerged as potent antitumor treatment modality. They are currently tested in many phase I, II and III clinical trials as single agents as wells as in combination schemes. They have demonstrated promising antitumor activity and favorable clinical outcome. Histone deacetylases (HDACs) are involved in the process of epigenetic regulation of gene expression. Epigenetic changes are believed to be crucial for the onset and progression of cancer and have recently gained remarkable attention. Since epigenetic regulation of gene expression is a reversible process, targeting histone deacetylases provides a good rationale for anticancer therapy. The acetylation status of histones regulates the organization of chromatin and the access of transcription factors. Moreover, functions of many non-histone proteins are controlled by acetylation. The broad and complicated influences of HDACi on various molecular processes may account for the observed pleiotropic effects. In this review we summarize recent advances in the understanding of biology of HDACs and mechanism of action of their inhibitors.
组蛋白去乙酰化酶抑制剂（HDACi）最近成为一种有效的抗肿瘤治疗方式。它们目前正在进行许多 I 期、II 期和 III 期临床试验，作为单一药物以及联合方案进行测试。它们已显示出有前途的抗肿瘤活性和良好的临床结果。组蛋白去乙酰化酶（HDACs）参与基因表达的表观遗传调控过程。表观遗传变化被认为是癌症发生和进展的关键因素，最近受到了极大的关注。由于基因表达的表观遗传调控是一个可逆的过程，靶向组蛋白去乙酰化酶为抗癌治疗提供了一个很好的理由。组蛋白的乙酰化状态调节染色质的组织和转录因子的进入。此外，许多非组蛋白的功能受乙酰化控制。HDACi 对各种分子过程的广泛而复杂的影响可能解释了观察到的多效性效应。在这篇综述中，我们总结了对 HDAC 生物学和抑制剂作用机制的理解的最新进展。
