Emerging EZH2 Inhibitors and Their Application in Lymphoma

被引：86

作者：

Lue, Jennifer K. ^{[1
]}

Amengual, Jennifer E. ^{[1
]}

机构：

[1] Columbia Univ, Med Ctr, Dept Med, Ctr Lymphoid Malignancies, 51 W 51st St,Suite 200, New York, NY 10019 USA

来源：

CURRENT HEMATOLOGIC MALIGNANCY REPORTS | 2018年 / 13卷 / 05期

关键词：

EZH2; Epigenetics; Non-Hodgkin lymphoma; inhibitors; Histone methylation; HISTONE METHYLTRANSFERASE EZH2; POLYCOMB GROUP PROTEIN; H3; LYSINE; 27; COMBINED EPIGENETIC THERAPY; AGGRESSIVE BREAST-CANCER; GROUP GENE EZH2; SELECTIVE-INHIBITION; INCREASED EXPRESSION; DEVELOPMENTAL GENES; SOMATIC MUTATIONS;

D O I：

10.1007/s11899-018-0466-6

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Purpose of ReviewEnhancer of Zeste Homolog 2 (EZH2) is histone methyltransferase and catalyzes the methylation of histone 3 lysine 27, a mark of transcriptional repression. Various studies have elucidated the complex role of EZH2 in both normal biology and tumorigenesis. Here, we critically review the emerging role of EZH2 in malignancies, the development of small molecule inhibitors of EZH2, and their application in lymphoma.Recent FindingsActivating mutations and overexpression of EZH2 are found in non-Hodgkin lymphoma (NHL). As a result, several EZH2 inhibitors have been developed and entered clinical investigation. Tazemetostat, first-in-class EZH2 inhibitor, demonstrated enhanced clinical activity in mutant follicular lymphoma and diffuse large B cell lymphoma.SummaryWith the early activity noted by tazemetostat in B cell lymphomas, the role of EZH2 inhibition in NHL is becoming more evident. This can be leveraged in future rationale combinations to enhance the activity of EZH2 inhibitors.

引用

页码：369 / 382

页数：14

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