Histone deacetylase inhibitors in cancer therapy.
Histone deacetylase inhibitors in cancer therapy.
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组蛋白脱乙酰基酶抑制剂在癌症治疗中。
DOI：
10.1097/cco.0b013e3283127095
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发表时间：
2008-11
影响因子：
3.4
通讯作者：
Trepel JB
中科院分区：
文献类型：
--
作者：
Lee MJ;Kim YS;Kummar S;Giaccone G;Trepel JB
本文综述了近年来组蛋白去乙酰化酶抑制剂（HDACi）在肿瘤治疗中的应用进展。最近，HDACi的临床研究有了显著的扩展。目前有11种HDACi在临床试验中，包括具有广谱HDAC亚型抑制活性的抑制剂以及具有亚型选择性的药物。目前正在进行70多项联合治疗试验。所涵盖的主要进展领域包括新的HDAC抑制剂进入临床开发，最近在了解HDACi抗癌活性的分子机制方面取得的进展，以及HDACi组合的临床前和临床更新。在审查期间，在理解HDACi作用机制、确定提高疗效和克服耐药性的合理组合方面取得了进展，并大大扩展了单药治疗和联合治疗方案中泛HDAC抑制性和亚型选择性抑制剂的临床开发。
The purpose of this review is to provide an overview of recent advances in the development of histone deacetylase inhibitors (HDACi) for the treatment of cancer. Recently, there has been a dramatic expansion of HDACi clinical investigation. There are now 11 HDACi in clinical trial, including inhibitors with a broad spectrum of HDAC isoform inhibitory activity as well as drugs with isoform selectivity. Over 70 combination therapy trials are in progress. Major areas of progress covered include the entry of new HDAC inhibitors into clinical development, recent progress in understanding of molecular mechanisms of HDACi anticancer activity, and a preclinical and clinical update on HDACi in combination. In the period under review there have been advances in understanding of HDACi mechanisms of action, identification of rational combinations that address increased efficacy and overcoming resistance, and greatly expanded clinical development of pan-HDAC-inhibitory and isoform-selective inhibitors in monotherapy and combination therapy protocols.