School of Computational and Integrative Sciences, Jawaharlal Nehru University, New Delhi, India.
Molecular Diagnostic and Personalised Therapeutics Unit, University of Ha'il, Ha'il-2440, Saudi Arabia.
Curr Drug Targets. 2021;22(11):1198-1206. doi: 10.2174/1389450122666210215111744.
Over the past several years, remarkable progress towards the recognition of new therapeutic targets in tumor cells has led to the discovery and development of newer scaffolds of anti-tumor drugs. The exploration and exploitation of epigenetic regulation in tumor cells are of immense importance to both the pharmaceutical and academic biomedical literatures. Epigenetic mechanisms are indispensable for the normal development and maintenance of tissue-specific gene expression. Disruption of epigenetic processes to eradicate tumor cells is among the most promising intervention for cancer control. Polycomb repressive complex 2 (PRC2), a complex that methylates lysine 27 of histone H3 to promote transcriptional silencing, is involved in orchestrating significant pathways in a cell. Overexpression of PRC2 has been found in a number of cancerous malignancies, making it a major target for anti-cancer therapy. Despite its well-understood molecular mechanism, hyperactivation and drug resistance mutations in its subunits have become a matter of discussion. This review outlines the current understanding of the components of PRC2 in active complex formation and assesses their potential as a promising therapeutic target for cancer therapy. We also review the effects of mutations in the PRC2 components, in the purview of human cancers. Finally, we discuss some of the current challenges for therapeutic drug designs targeting the PRC2 complex.
在过去的几年中，在识别肿瘤细胞中的新治疗靶点方面取得了显著进展，导致了新型抗肿瘤药物支架的发现和发展。肿瘤细胞中表观遗传调控的探索和开发对制药和学术生物医学文献都具有重要意义。表观遗传机制对于组织特异性基因表达的正常发育和维持是不可或缺的。破坏表观遗传过程以消除肿瘤细胞是癌症控制最有前途的干预措施之一。多梳抑制复合物 2 (PRC2) 是一种将组蛋白 H3 的赖氨酸 27 甲基化以促进转录沉默的复合物，参与协调细胞中的重要途径。已经在许多癌症中发现 PRC2 的过表达，使其成为抗癌治疗的主要靶点。尽管其分子机制已经得到很好的理解，但它的亚基的过度激活和药物抗性突变已成为讨论的话题。本综述概述了 PRC2 在活性复合物形成中的组成部分的当前理解，并评估了它们作为癌症治疗有希望的治疗靶标的潜力。我们还综述了 PRC2 成分突变在人类癌症中的作用。最后，我们讨论了针对 PRC2 复合物的治疗药物设计的一些当前挑战。
