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乳腺癌中的表观遗传调控:治疗意义中的新兴范例。

Epigenetic Modulations in Breast Cancer: An Emerging Paradigm in Therapeutic Implications.

机构信息

Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, 781039 Guwahati, Assam, India.

Centre for Nanotechnology, Indian Institute of Technology Guwahati, 781039 Guwahati, Assam, India.

出版信息

Front Biosci (Landmark Ed). 2024 Aug 19;29(8):287. doi: 10.31083/j.fbl2908287.

Abstract

Breast cancer, a heterogeneous and intricate disease, ranks among the leading causes of mortality in women. Restricted therapeutic choices, drug resistance, recurrence, and metastasis are the predominant conditions that lead to mortality. Accumulating evidence has shown breast cancer initiation and progression happen through a multifaceted and intricate process that involves numerous genetic and epigenetic alterations. The modulation of gene expression through epigenetic modifications, encompassing DNA methylation, histone alterations, and non-coding RNA regulation, has emerged as a fascinating field that represents a new avenue for breast cancer therapy. This review emphasizes various aberrant epigenetic regulations implicated in the onset and advancement of breast cancer. The critical epigenetic modifications closely associated with estrogen signaling, epithelial-to-mesenchymal transition (EMT), cancer stemness, and drug resistance have been discussed extensively. Moreover, it highlights current epi-drugs, including DNA modifying agents, histone acetyltransferase inhibitors, histone deacetylase inhibitors, histone methyltransferase inhibitors, and histone demethyltransferase inhibitors used for breast cancer treatment. Nonetheless, we described current investigations pertaining to combination therapy employing epi-drugs and future challenges.

摘要

乳腺癌是一种异质性和复杂的疾病,是女性死亡的主要原因之一。治疗选择有限、耐药性、复发和转移是导致死亡的主要因素。越来越多的证据表明,乳腺癌的发生和发展是通过一个多方面和复杂的过程,涉及许多遗传和表观遗传的改变。通过表观遗传修饰来调节基因表达,包括 DNA 甲基化、组蛋白改变和非编码 RNA 调节,已成为一个引人入胜的领域,为乳腺癌治疗提供了新的途径。本综述强调了各种异常的表观遗传调控在乳腺癌的发生和发展中的作用。本文还详细讨论了与雌激素信号、上皮间质转化(EMT)、癌症干性和耐药性密切相关的关键表观遗传修饰。此外,还强调了目前用于乳腺癌治疗的 epi 药物,包括 DNA 修饰剂、组蛋白乙酰转移酶抑制剂、组蛋白去乙酰化酶抑制剂、组蛋白甲基转移酶抑制剂和组蛋白去甲基化酶抑制剂。然而,我们也描述了当前关于联合治疗的研究,包括 epi 药物和未来的挑战。

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