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组蛋白去乙酰化酶抑制剂在癌症表观遗传靶点治疗中的研究进展

Research Advances in the Use of Histone Deacetylase Inhibitors for Epigenetic Targeting of Cancer.

机构信息

School of Pharmacy, Jilin Medical University, Jilin, China.

Center for Biomaterials, Jilin Medical University, Jilin, China.

出版信息

Curr Top Med Chem. 2019;19(12):995-1004. doi: 10.2174/1568026619666190125145110.

Abstract

The causes and progression of cancer are controlled by epigenetic processes. The mechanisms involved in epigenetic regulation of cancer development, gene expression, and signaling pathways have been studied. Histone deacetylases (HDACs) have a major impact on chromatin remodeling and epigenetics, making their inhibitors a very interesting area of cancer research. This review comprehensively summarizes the literature regarding HDAC inhibitors (HDACis) as an anticancer treatment published in the past few years. In addition, we explain the mechanisms of their therapeutic effects on cancer. An analysis of the beneficial characteristics and drawbacks of HDACis also is presented, which will assist preclinical and clinical researchers in the design of future experiments to improve the therapeutic efficacy of these drugs and circumvent the challenges in the path of successful epigenetic therapy. Future therapeutic strategies may include a combination of HDACis and chemotherapy or other inhibitors to target multiple oncogenic signaling pathways.

摘要

癌症的病因和发展过程受到表观遗传过程的控制。目前已经研究了参与癌症发生、基因表达和信号通路的表观遗传调控的机制。组蛋白去乙酰化酶 (HDACs) 对染色质重塑和表观遗传有重大影响,因此它们的抑制剂是癌症研究中一个非常有趣的领域。本综述全面总结了过去几年中关于作为抗癌治疗的 HDAC 抑制剂 (HDACi) 的文献。此外,我们还解释了它们对癌症的治疗效果的机制。还分析了 HDACi 的有益特征和缺点,这将有助于临床前和临床研究人员设计未来的实验,以提高这些药物的治疗效果,并克服成功的表观遗传治疗道路上的挑战。未来的治疗策略可能包括 HDACi 与化疗或其他抑制剂联合使用,以靶向多个致癌信号通路。

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