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组蛋白去乙酰化酶抑制剂在血液系统恶性肿瘤治疗中的应用。

Histone deacetylase inhibitors in the treatment of hematological malignancies.

机构信息

Department Scienze Farmaceutiche e Biomediche Università di Salerno Via Ponte Don Melillo 84084 Fisciano, Salerno, Italy.

出版信息

Mini Rev Med Chem. 2011 Jun;11(6):519-27. doi: 10.2174/138955711795843347.

Abstract

Histone deacetylases (HDACs) play a central role in the epigenetic regulation of gene expression. Aberrant activity of HDACs has been found in several human cancers leading to the development of HDAC inhibitors (HDACi) as anti-tumors drugs. In fact, over the last years, a number of HDACi have been evaluated in clinical trials; these drugs have the common ability to hyperacetylate both histone and non-histone targets, resulting in a variety of effects on both cancer cells and immune responses. Clinical trials of HDACi conducted in solid tumors and hematological malignancies have shown a better clinical efficacy of these drugs in hematological malignancies. In this review, will be highlighted the mechanisms of action underlying the clinical responses obtained with these drugs and the doubts regarding the use of HDACi in cancer therapy.

摘要

组蛋白去乙酰化酶(HDACs)在基因表达的表观遗传调控中发挥核心作用。在几种人类癌症中发现了 HDACs 的异常活性,导致了 HDAC 抑制剂(HDACi)作为抗肿瘤药物的发展。事实上,在过去的几年中,已经有许多 HDACi 在临床试验中进行了评估;这些药物具有使组蛋白和非组蛋白靶标过度乙酰化的共同能力,从而对癌细胞和免疫反应产生多种影响。在实体瘤和血液恶性肿瘤中进行的 HDACi 临床试验表明,这些药物在血液恶性肿瘤中的临床疗效更好。在这篇综述中,将强调这些药物获得临床反应的作用机制,以及关于在癌症治疗中使用 HDACi 的疑虑。

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