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RAF 抑制剂在 BRAF 突变型脑胶质瘤治疗中的评价。

A critical review of RAF inhibitors in BRAF-mutated glioma treatment.

机构信息

Université Saint-Joseph de Beyrouth, Beyrouth, 11-5076, Lebanon.

Department of Pathology, Université Saint-Joseph de Beyrouth, Beyrouth, 11-5076, Lebanon.

出版信息

Pharmacogenomics. 2024;25(7):343-355. doi: 10.1080/14622416.2024.2355859. Epub 2024 Jun 3.

Abstract

BRAF gliomas have garnered significant attention in research due to the lack of effective treatments and their notable incidence, constituting 3% of all gliomas. This underlines the importance of investigating this area and the impact that targeted therapies could hold. This review discusses the development of targeted therapies for these tumors, examining the effectiveness of first-generation BRAF inhibitors such as Vemurafenib, Dabrafenib and Encorafenib, while addressing the challenges posed by paradoxical ERK activation. The advent of pan-RAF inhibitors, notably Tovorafenib, offers a promising advance, demonstrating enhanced efficacy and better penetration of the blood-brain barrier, without the issue of paradoxical activation. Nevertheless, continued research is essential to refine therapeutic strategies for BRAF-mutated gliomas, given the evolving nature of targeted therapy development.

摘要

BRAF 神经胶质瘤由于缺乏有效治疗方法且发病率较高(占所有神经胶质瘤的 3%)而受到研究人员的广泛关注。这凸显了研究这一领域的重要性,以及靶向治疗可能产生的影响。本综述讨论了针对这些肿瘤的靶向治疗方法的发展,研究了第一代 BRAF 抑制剂(如维莫非尼、达拉非尼和恩考芬尼)的有效性,同时解决了 ERK 激活悖论带来的挑战。泛 RAF 抑制剂,特别是托沃拉非尼的出现,提供了一个有希望的进展,显示出增强的疗效和更好的血脑屏障穿透性,而没有激活悖论的问题。然而,鉴于靶向治疗开发的不断发展,为了完善 BRAF 突变型神经胶质瘤的治疗策略,仍需要继续研究。

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