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癌症表观遗传学:过去、现在和未来。

Cancer epigenetics: Past, present and future.

机构信息

Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea.

Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea; KAIST Institute for the BioCentury, Cancer Metastasis Control Center, Daejeon, Republic of Korea.

出版信息

Semin Cancer Biol. 2022 Aug;83:4-14. doi: 10.1016/j.semcancer.2021.03.025. Epub 2021 Mar 31.

Abstract

Cancer was thought to be caused solely by genetic mutations in oncogenes and tumor suppressor genes. In the last 35 years, however, epigenetic changes have been increasingly recognized as another primary driver of carcinogenesis and cancer progression. Epigenetic deregulation in cancer often includes mutations and/or aberrant expression of chromatin-modifying enzymes, their associated proteins, and even non-coding RNAs, which can alter chromatin structure and dynamics. This leads to changes in gene expression that ultimately contribute to the emergence and evolution of cancer cells. Studies of the deregulation of chromatin modifiers in cancer cells have reshaped the way we approach cancer and guided the development of novel anticancer therapeutics that target epigenetic factors. There remain, however, a number of unanswered questions in this field that are the focus of present research. Areas of particular interest include the actions of emerging classes of epigenetic regulators of carcinogenesis and the tumor microenvironment, as well as epigenetic tumor heterogeneity. In this review, we discuss past findings on epigenetic mechanisms of cancer, current trends in the field of cancer epigenetics, and the directions of future research that may lead to the identification of new prognostic markers for cancer and the development of more effective anticancer therapeutics.

摘要

癌症曾被认为仅由癌基因和肿瘤抑制基因中的遗传突变引起。然而,在过去的 35 年中,表观遗传变化已越来越被认为是致癌和癌症进展的另一个主要驱动因素。癌症中的表观遗传失调通常包括染色质修饰酶及其相关蛋白的突变和/或异常表达,甚至包括非编码 RNA,这些都可以改变染色质结构和动力学。这导致基因表达的变化,最终导致癌细胞的出现和演变。对癌细胞中染色质修饰物失调的研究改变了我们治疗癌症的方式,并指导了针对表观遗传因子的新型抗癌治疗药物的开发。然而,该领域仍存在许多悬而未决的问题,这些问题是目前研究的重点。特别感兴趣的领域包括新兴的致癌表观遗传调节剂和肿瘤微环境以及表观遗传肿瘤异质性的作用。在这篇综述中,我们讨论了癌症的表观遗传机制的过去发现、癌症表观遗传学领域的当前趋势,以及未来可能导致鉴定癌症新预后标志物和开发更有效的抗癌治疗药物的研究方向。

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