Endogenous modulators and pharmacological inhibitors of histone deacetylases in cancer therapy.
Endogenous modulators and pharmacological inhibitors of histone deacetylases in cancer therapy.
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DOI：
10.1038/onc.2011.267
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发表时间：
2012-02-02
期刊：
影响因子：
8
通讯作者：
Grant, S.
中科院分区：
文献类型：
--
作者：
Spiegel, S.;Milstien, S.;Grant, S.
I类组蛋白去乙酰化酶HDAC 1和HDAC 2属于11种锌依赖性人类HDAC家族，并且在许多癌症中过表达。这些HDAC的抑制剂现在在临床试验中显示出对几种类型癌症的活性。本文综述了HDACi作用的临床和临床前研究进展，重点是与常规或其他靶向药物合理组合的影响。我们将探讨HDAC作用的分子机制以及这些作用与癌症的关系。我们还将审查新的证据表明，HDACs是直接的细胞内目标的有效的鞘脂介质鞘氨醇-1-磷酸（S1 P），第一个确定的内源性核调节这些酶，连接鞘脂代谢在细胞核中的染色质重塑和基因表达的表观遗传调控。了解内源性分子如何在体内调节HDAC活性可能有助于寻找更安全，更有效的抗癌药物，能够以高度特异性的方式干扰HDAC功能。
The class I histone deacetylases HDAC1 and HDAC2 belong to a family of 11 zinc-dependent human HDACs and are overexpressed in many cancers. Inhibitors of these HDACs now in clinical trials show activity against several types of cancers. This review is focuse on recent advances in both clinical and preclinical efforts to understand the basis for HDACi actions, with an emphasis on implications for rational combinations with conventional or other targeted agents. We will address new perspectives on the molecular mechanisms by which HDACs act and how these actions relate to cancer. We will also review new evidence demonstrating that HDACs are direct intracellular targets of the potent sphingolipid mediator sphingosine-1-phosphate (S1P), the first identified endogenous nuclear regulator of these enzymes, linking sphingolipid metabolism in the nucleus to remodeling of chromatin and epigenetic regulation of gene expression. Understanding how endogenous molecules regulate HDAC activity in vivo may facilitate the search for safer and more effective anti-cancer drugs capable of interfering with HDAC functions in a highly specific manner.
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DOI：
10.1111/j.1349-7006.2001.tb02153.x
发表时间：
2001-12
期刊：
Japanese journal of cancer research : Gann
影响因子：
--
作者：
Choi JH;Kwon HJ;Yoon BI;Kim JH;Han SU;Joo HJ;Kim DY
通讯作者：
Kim DY
影响因子：
11.2
作者：
Dai CL;Tiwari AK;Wu CP;Su XD;Wang SR;Liu DG;Ashby CR Jr;Huang Y;Robey RW;Liang YJ;Chen LM;Shi CJ;Ambudkar SV;Chen ZS;Fu LW
通讯作者：
Fu LW
影响因子：
46.9
作者：
Bantscheff, Marcus;Hopf, Carsten;Drewes, Gerard
通讯作者：
Drewes, Gerard
影响因子：
30.8
作者：
Cameron, EE;Bachman, KE;Baylin, SB
通讯作者：
Baylin, SB
Vorinostat与Bortezomib结合的I阶段研究，用于复发和难治性多发性骨髓瘤。
影响因子：
11.5
作者：
Badros, Ashraf;Burger, Angelika M.;Philip, Sunita;Niesvizky, Ruben;Kolla, Sarah S.;Goloubeva, Olga;Harris, Carolynn;Zwiebel, James;Wright, John J.;Espinoza-Delgado, Igor;Baer, Maria R.;Holleran, Julianne L.;Egorin, Merrill J.;Grant, Steven
通讯作者：
Grant, Steven