Wu Donglu, Qiu Ye, Jiao Yunshuang, Qiu Zhidong, Liu Da
School of Clinical Medical, Changchun University of Chinese Medicine, Changchun, China.
Key Laboratory of Effective Components of Traditional Chinese Medicine, Changchun, China.
Front Oncol. 2020 Nov 11;10:560487. doi: 10.3389/fonc.2020.560487. eCollection 2020.
Evidence for research over the past decade shows that epigenetic regulation mechanisms run through the development and prognosis of tumors. Therefore, small molecular compounds targeting epigenetic regulation have become a research hotspot in the development of cancer therapeutic drugs. According to the obvious abnormality of histone acetylation when tumors occur, it suggests that histone acetylation modification plays an important role in the process of tumorigenesis. Currently, as a new potential anti-cancer therapeutic drugs, many active small molecules that target histone acetylation regulatory enzymes or proteins such as histone deacetylases (HDACs), histone acetyltransferase (HATs) and bromodomains (BRDs) have been developed to restore abnormal histone acetylation levels to normal. In this review, we will focus on summarizing the changes of histone acetylation levels during tumorigenesis, as well as the possible pharmacological mechanisms of small molecules that target histone acetylation in cancer treatment.
过去十年的研究证据表明，表观遗传调控机制贯穿肿瘤的发生发展及预后过程。因此，靶向表观遗传调控的小分子化合物已成为癌症治疗药物研发的热点。肿瘤发生时组蛋白乙酰化存在明显异常，这表明组蛋白乙酰化修饰在肿瘤发生过程中起重要作用。目前，作为新型潜在抗癌治疗药物，已研发出许多靶向组蛋白乙酰化调控酶或蛋白（如组蛋白去乙酰化酶（HDACs）、组蛋白乙酰转移酶（HATs）和溴结构域（BRDs））的活性小分子，以将异常的组蛋白乙酰化水平恢复正常。在本综述中，我们将重点总结肿瘤发生过程中组蛋白乙酰化水平的变化，以及靶向组蛋白乙酰化的小分子在癌症治疗中的可能药理机制。
