Tazemetostat for advanced epithelioid sarcoma: current status and future perspectives.

IF 3 4区 医学 Q2 ONCOLOGY Future oncology Pub Date : 2021-04-01 Epub Date: 2020-12-08 DOI:10.2217/fon-2020-0781
Noemi Simeone, Anna Maria Frezza, Nadia Zaffaroni, Silvia Stacchiotti
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引用次数: 14

Abstract

Epithelioid sarcoma (ES) is an aggressive ultra-rare soft-tissue sarcoma marked by SMARCB1/INI1 deficiency. SMARCB1/INI1 deficiency leads to elevated expression of EZH2, a component of polycomb repressive complex 2, which mediates gene silencing by catalyzing H3K27me3. Tazemetostat is an oral, SAM-competitive inhibitor of EZH2, whose blockade prevents the methylation of histone H3K27, thus decreasing the growth of EZH2 mutated or over-expressing cancer cells. Tazemetostat has been approved for the treatment of patients aged 16 years and older with metastatic or advanced ES not eligible for complete resection, based on the positive results of a single-arm Phase II basket study. Tazemetostat though represents a new treatment option for ES patients, although clinical/molecular predictors of response are still to be identified. The combination of tazemetostat with other drugs like doxorubicin and immunotherapeutic agents is currently under investigation in ES patients.

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他泽美他汀治疗晚期上皮样肉瘤:现状和未来展望。
上皮样肉瘤(ES)是一种侵袭性的超罕见软组织肉瘤,其特征是SMARCB1/INI1缺乏。SMARCB1/INI1缺陷导致EZH2表达升高,EZH2是多梳抑制复合体2的一个组成部分,通过催化H3K27me3介导基因沉默。Tazemetostat是一种口服的、sam竞争的EZH2抑制剂,其阻断可阻止组蛋白H3K27的甲基化,从而降低EZH2突变或过表达癌细胞的生长。Tazemetostat已被批准用于治疗16岁及以上不适合完全切除的转移性或晚期ES患者,基于单臂II期一揽子研究的阳性结果。他zemetostat虽然代表了ES患者的一种新的治疗选择,但临床/分子反应预测因素仍有待确定。他泽美他汀与其他药物如阿霉素和免疫治疗剂联合应用于ES患者目前正在研究中。
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来源期刊
Future oncology
Future oncology ONCOLOGY-
CiteScore
5.40
自引率
3.00%
发文量
335
审稿时长
4-8 weeks
期刊介绍: Future Oncology (ISSN 1479-6694) provides a forum for a new era of cancer care. The journal focuses on the most important advances and highlights their relevance in the clinical setting. Furthermore, Future Oncology delivers essential information in concise, at-a-glance article formats - vital in delivering information to an increasingly time-constrained community. The journal takes a forward-looking stance toward the scientific and clinical issues, together with the economic and policy issues that confront us in this new era of cancer care. The journal includes literature awareness such as the latest developments in radiotherapy and immunotherapy, concise commentary and analysis, and full review articles all of which provide key findings, translational to the clinical setting.
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