Mio Catia, Bulotta Stefania, Russo Diego, Damante Giuseppe
Department of Medical Area, University of Udine, 33100 Udine, Italy.
Department of Health Sciences, "Magna Graecia" University of Catanzaro, 88100 Catanzaro, Italy.
Cancers (Basel). 2019 Jan 9;11(1):61. doi: 10.3390/cancers11010061.
The epigenetic machinery deputed to control histone post-translational modifications is frequently dysregulated in cancer cells. With epigenetics being naturally reversible, it represents a good target for therapies directed to restore normal gene expression. Since the discovery of Bromodomain and Extra Terminal (BET) inhibitors, a great effort has been spent investigating the effects of chromatin readers' inhibition, specifically the class of proteins assigned to bind acetylated and methylated residues. So far, focused studies have been produced on epigenetic regulation, dissecting a specific class of epigenetic-related proteins or investigating epigenetic therapy in a specific tumor type. In this review, recent steps toward drug discovery on the different classes of chromatin readers have been outlined, highlighting the pros and cons of current therapeutic approaches.
负责控制组蛋白翻译后修饰的表观遗传机制在癌细胞中常常失调。由于表观遗传学具有天然的可逆性，它是旨在恢复正常基因表达的治疗方法的良好靶点。自发现溴结构域和额外末端（BET）抑制剂以来，人们在研究染色质读取器抑制的作用方面付出了巨大努力，特别是研究那些负责结合乙酰化和甲基化残基的蛋白质类别。到目前为止，已经针对表观遗传调控开展了重点研究，剖析了特定类别的表观遗传相关蛋白，或在特定肿瘤类型中研究表观遗传治疗。在这篇综述中，概述了在不同类别的染色质读取器药物研发方面的最新进展，强调了当前治疗方法的优缺点。
