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癌症表观遗传学:新疗法与新挑战。

Cancer epigenetics: new therapies and new challenges.

作者信息

Hatzimichael Eleftheria, Crook Tim

机构信息

Department of Haematology, University Hospital of Ioannina, St. Niarchou Avenue, 45110 Ioannina, Greece ; Computational Medicine Center, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USA.

出版信息

J Drug Deliv. 2013;2013:529312. doi: 10.1155/2013/529312. Epub 2013 Feb 26.

Abstract

Cancer is nowadays considered to be both a genetic and an epigenetic disease. The most well studied epigenetic modification in humans is DNA methylation; however it becomes increasingly acknowledged that DNA methylation does not work alone, but rather is linked to other modifications, such as histone modifications. Epigenetic abnormalities are reversible and as a result novel therapies that work by reversing epigenetic effects are being increasingly explored. The biggest clinical impact of epigenetic modifying agents in neoplastic disorders thus far has been in haematological malignancies, and the efficacy of DNMT inhibitors and HDAC inhibitors in blood cancers clearly attests to the principle that therapeutic modification of the cancer cell epigenome can produce clinical benefit. This paper will discuss the most well studied epigenetic modifications and how these are linked to cancer, will give a brief overview of the clinical use of epigenetics as biomarkers, and will focus in more detail on epigenetic drugs and their use in solid and blood cancers.

摘要

如今,癌症被认为既是一种基因疾病,也是一种表观遗传疾病。在人类中研究最深入的表观遗传修饰是DNA甲基化;然而,人们越来越认识到,DNA甲基化并非单独起作用,而是与其他修饰相关联,比如组蛋白修饰。表观遗传异常是可逆的,因此,通过逆转表观遗传效应起作用的新型疗法正在得到越来越多的探索。到目前为止,表观遗传修饰剂在肿瘤性疾病中的最大临床影响体现在血液系统恶性肿瘤方面,DNA甲基转移酶抑制剂和组蛋白去乙酰化酶抑制剂在血癌中的疗效清楚地证明了对癌细胞表观基因组进行治疗性修饰可产生临床益处这一原理。本文将讨论研究最深入的表观遗传修饰及其与癌症的关联,简要概述表观遗传学作为生物标志物的临床应用,并更详细地聚焦于表观遗传药物及其在实体癌和血癌中的应用。

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