Ovarian cancer is the fifth leading cause of cancer-related deaths in females in the United States. There were an estimated 22,440 new cases and 14,080 deaths due to ovarian cancer in 2017. Most patients present with advanced-stage disease, revealing the urgent need for new therapeutic strategies targeting pathways of tumorigenesis and chemotherapy resistance. While multiple genomic changes contribute to the progression of this aggressive disease, it has become increasingly evident that epigenetic events play a pivotal role in ovarian cancer development. One of the well-studied epigenetic modifiers, the histone methyltransferase EZH2, is a member of polycomb repressive complex 2 (PRC2) and is commonly involved in transcriptional repression. EZH2 is the enzymatic catalytic subunit of the PRC2 complex that can alter gene expression by trimethylating lysine 27 on histone 3 (H3K27). In ovarian cancer, EZH2 is commonly overexpressed and therefore potentially serves as an effective therapeutic target. Multiple small-molecule inhibitors are being developed to target EZH2, which are now in clinical trials. Thus, in this review, we highlight the progress made in EZH2-related research in ovarian cancer and discuss the potential utility of targeting EZH2 with available small-molecule inhibitors for ovarian cancer. Mol Cancer Ther; 17(3); 591–602. ©2018 AACR.

中文翻译：

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组蛋白甲基转移酶 EZH2：卵巢癌的治疗靶点

卵巢癌是美国女性癌症相关死亡的第五大原因。2017 年估计有 22,440 例新发病例和 14,080 例死于卵巢癌。大多数患者都患有晚期疾病，这表明迫切需要针对肿瘤发生和化疗耐药途径的新治疗策略。虽然多种基因组变化有助于这种侵袭性疾病的进展，但越来越明显的是，表观遗传事件在卵巢癌的发展中起着关键作用。研究充分的表观遗传修饰因子之一，组蛋白甲基转移酶 EZH2，是多梳抑制复合物 2 (PRC2) 的成员，通常参与转录抑制。EZH2 是PRC2 复合物的酶催化亚基，可以通过三甲基化组蛋白3 (H3K27) 上的赖氨酸27 来改变基因表达。在卵巢癌中，EZH2 通常过度表达，因此有可能作为有效的治疗靶点。针对 EZH2 的多种小分子抑制剂正在开发中，目前正在临床试验中。因此，在这篇综述中，我们重点介绍了 EZH2 相关卵巢癌研究取得的进展，并讨论了用可用的小分子抑制剂靶向 EZH2 治疗卵巢癌的潜在效用。摩尔癌症治疗; 17(3); 591-602。©2018 AACR。现在正在进行临床试验。因此，在这篇综述中，我们重点介绍了 EZH2 相关卵巢癌研究的进展，并讨论了用可用的小分子抑制剂靶向 EZH2 治疗卵巢癌的潜在效用。摩尔癌症治疗; 17(3); 591-602。©2018 AACR。现在正在进行临床试验。因此，在这篇综述中，我们重点介绍了 EZH2 相关卵巢癌研究的进展，并讨论了用可用的小分子抑制剂靶向 EZH2 治疗卵巢癌的潜在效用。摩尔癌症治疗; 17(3); 591-602。©2018 AACR。