Liu Kai-Lu, Zhu Kongkai, Zhang Hua
School of Biological Science and Technology, University of Jinan Jinan 250022 China
RSC Med Chem. 2021 Oct 21;13(1):39-53. doi: 10.1039/d1md00274k. eCollection 2022 Jan 27.
Polycomb repressive complex 2 (PRC2) catalyzes the methylation of histone H3 lysine 27 (H3K27) and the enrichment of its catalytic product H3K27me3 is responsible for the silencing of tumor suppressor genes and the blocking of transcripts related to immunity and cell terminal differentiation. Aberrations of PRC2 components, such as mutation and overexpression, have been observed in various cancers, which makes PRC2 a potential therapeutic target for cancer. Up to now, targeting the enhancer of zeste homolog 2 (EZH2), the catalytic subunit of PRC2, represents the main strategy in the development of PRC2 inhibitors. Although significant progress has been made, new problems also emerge, the drug resistance caused by secondary mutations. In recent years, more and more efforts have shifted to another new strategy - targeting embryonic ectoderm development (EED) to disrupt its major interactions with other components, which are necessary to the PRC2 function, and some promising results have been obtained. This review summarizes the recent development of EED inhibitors as possible chemotherapy for cancer treatment, which could help accelerate future related research work.
多梳抑制复合物2（PRC2）催化组蛋白H3赖氨酸27（H3K27）的甲基化，其催化产物H3K27me3的富集导致肿瘤抑制基因沉默，并阻断与免疫和细胞终末分化相关的转录本。在各种癌症中均观察到PRC2组分的异常，如突变和过表达，这使得PRC2成为癌症潜在的治疗靶点。到目前为止，靶向PRC2的催化亚基zeste同源物2（EZH2）增强子是PRC2抑制剂开发的主要策略。尽管已取得显著进展，但新问题也随之出现，即由二次突变引起的耐药性。近年来，越来越多的努力转向另一种新策略——靶向胚胎外胚层发育（EED）以破坏其与PRC2功能所必需的其他组分的主要相互作用，并已取得了一些有前景的结果。本综述总结了EED抑制剂作为癌症治疗潜在化疗药物的最新进展，这有助于加速未来相关研究工作。
