Department of Molecular Biology and Biochemistry, Simon Fraser University, Vancouver, BC, Canada; and.
Jewish General Hospital, McGill University, Montreal, QC, Canada.
Blood Adv. 2021 Apr 27;5(8):2256-2263. doi: 10.1182/bloodadvances.2020002773.
Tazemetostat represents the first epigenetic therapy approved for the treatment of follicular lymphoma (FL). It inhibits the activity of the enhancer of zeste homolog 2 (EZH2) histone methyltransferase, the first of a multitude of epigenetic regulators that have been identified as recurrently mutated in FL and germinal center diffuse large B-cell lymphoma. In this review, we discuss the initial discovery and ongoing exploration of the functional role of EZH2 mutations in lymphomagenesis. We also explore the path from the preclinical development of tazemetostat to its approval for the treatment of relapsed FL, and potential future therapeutic applications. We discuss the clinical data that led to the approval of tazemetostat and ongoing research into the function of EZH2 and of tazemetostat in lymphomas that derive from the germinal center, which could increase the applicability of this drug in the future.
他泽司他丁是首个获批用于治疗滤泡性淋巴瘤（FL）的表观遗传学疗法。它能抑制增强子结合锌指蛋白 2（EZH2）组蛋白甲基转移酶的活性，EZH2 是众多已被鉴定为在 FL 和生发中心弥漫性大 B 细胞淋巴瘤中频繁突变的表观遗传调控因子之一。在这篇综述中，我们讨论了 EZH2 突变在淋巴瘤发生中的最初发现和正在进行的功能作用研究。我们还探讨了从他泽司他丁的临床前开发到其获批用于治疗复发 FL 以及潜在未来治疗应用的过程。我们讨论了导致他泽司他丁获批的临床数据，以及正在进行的关于 EZH2 功能和他泽司他丁在生发中心起源的淋巴瘤中的作用的研究，这可能会增加该药物在未来的适用性。
