Title:New Framework for the Discovery of PRC2 Inhibitors: Epigenetic Drugs
Volume: 22
Issue: 11
关键词:
癌症，表观遗传学，PRC2，组蛋白甲基化，药物开发，治疗性。
摘要: 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.
