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米非司酮在高级别胶质瘤治疗中的新用途

Mifepristone Repurposing in Treatment of High-Grade Gliomas.

作者信息

Llaguno-Munive Monserrat, Vazquez-Lopez Maria Ines, Jurado Rafael, Garcia-Lopez Patricia

机构信息

Laboratorio de Farmacología, Subdirección de Investigación Básica, Instituto Nacional de Cancerología, Mexico City, Mexico.

出版信息

Front Oncol. 2021 Feb 18;11:606907. doi: 10.3389/fonc.2021.606907. eCollection 2021.

Abstract

Glioma is the most common and aggressive primary tumor of the central nervous system. The standard treatment for malignant gliomas is surgery followed by chemoradiotherapy. Unfortunately, this treatment has not produced an adequate patient response, resulting in a median survival time of 12-15 months and a 5-year overall survival of <5%. Although new strategies have been sought to enhance patient response, no significant increase in the global survival of glioma patients has been achieved. The option of developing new drugs implies a long and costly process, making drug repurposing a more practical alternative for improving glioma treatment. In the last few years, researchers seeking more effective cancer therapy have pursued the possibility of using anti-hormonal agents, such as mifepristone. The latter drug, an antagonist for progesterone and glucocorticoid receptors, has several attractive features: anti-tumor activity, low cytotoxicity to healthy cells, and modulation of the chemosensitivity of several cancer cell lines . Hence, the addition of mifepristone to temozolomide-based glioblastoma chemotherapy may lead to a better patient response. The mechanisms by which mifepristone enhances glioma treatment are not yet known. The current review aims to discuss the potential role of mifepristone as an adjuvant drug for the treatment of high-grade gliomas.

摘要

胶质瘤是中枢神经系统最常见且侵袭性最强的原发性肿瘤。恶性胶质瘤的标准治疗方法是手术,随后进行放化疗。不幸的是,这种治疗方法并未使患者产生足够的反应,导致中位生存时间为12 - 15个月,5年总生存率<5%。尽管一直在寻求新的策略来提高患者的反应,但胶质瘤患者的总体生存率并未显著提高。开发新药意味着一个漫长且成本高昂的过程,因此药物重新利用成为改善胶质瘤治疗的更实际选择。在过去几年中,寻求更有效癌症治疗方法的研究人员一直在探索使用抗激素药物(如米非司酮)的可能性。后一种药物是孕酮和糖皮质激素受体的拮抗剂,具有几个吸引人的特性:抗肿瘤活性、对健康细胞的低细胞毒性以及对几种癌细胞系化学敏感性的调节。因此,在基于替莫唑胺的胶质母细胞瘤化疗中添加米非司酮可能会使患者产生更好的反应。米非司酮增强胶质瘤治疗的机制尚不清楚。本综述旨在讨论米非司酮作为治疗高级别胶质瘤辅助药物的潜在作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77d8/7930566/355b33ae748f/fonc-11-606907-g001.jpg

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