Histone Methyltransferase EZH2: A Therapeutic Target for Ovarian Cancer.
Histone Methyltransferase EZH2: A Therapeutic Target for Ovarian Cancer.
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DOI：
10.1158/1535-7163.mct-17-0437
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发表时间：
2018-03
影响因子：
5.7
通讯作者：
Arend RC
中科院分区：
文献类型：
--
作者：
Jones BA;Varambally S;Arend RC
卵巢癌是美国女性癌症相关死亡的第五大原因。预计2017年将有约22，440例新病例和14，080例因卵巢癌死亡。大多数患者表现为晚期疾病，这表明迫切需要针对肿瘤发生和化疗耐药性途径的新治疗策略。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。其中一个被充分研究的表观遗传修饰因子，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，其可以通过使组蛋白3（H3K27）上的赖氨酸27三甲基化来改变基因表达。在卵巢癌中，EZH2通常过表达，因此可能作为有效的治疗靶点。正在开发多种小分子抑制剂以靶向EZH2，目前正在进行临床试验。因此，在这篇综述中，我们重点介绍了EZH2在卵巢癌中的相关研究进展，并讨论了靶向EZH2的小分子抑制剂对卵巢癌的潜在效用。
Ovarian cancer is the fifth leading cause of cancer-related deaths in females in the United States. It is anticipated that there will be about 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.