三氟拉嗪在胶质母细胞瘤治疗中的应用

IF 19.9 1区 医学 Q1 PHARMACOLOGY & PHARMACY
Trends in pharmacological sciences Pub Date : 2025-05-01 Epub Date: 2025-04-28 DOI:10.1016/j.tips.2025.03.005
Manam Inushi De Silva, Hui K Gan, Cedric Bardy
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引用次数: 0

摘要

胶质母细胞瘤(GBM)由于其异质性和可塑性,特别是与脑微环境的相互作用,导致治疗耐药性,仍然是一个治疗挑战。最近的临床前证据表明,三氟拉嗪(TFP)抑制治疗诱导的肿瘤细胞恶性重编程,可能有助于降低肿瘤的可塑性。TFP靶向钙调蛋白、多巴胺受体和应激反应蛋白(核蛋白1,NUPR1)。通过这些机制,在异种移植动物模型中,TFP已被证明可以减少肿瘤生长,使肿瘤对放化疗敏感,并延长存活时间。TFP作为抗精神病药物的临床安全性众所周知,最近的临床前证据进一步表明,尽管TFP对多巴胺受体有短暂的功能影响,但对健康神经元和神经胶质细胞的毒性较低。本意见探讨了TFP的作用机制和临床活性,以评估其作为GBM重新治疗选择的适用性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Repurposing trifluoperazine for glioblastoma treatment.

Glioblastoma (GBM) remains a therapeutic challenge due to its heterogeneity and plasticity, which drive treatment resistance, especially when compounded by interactions with the brain microenvironment. Recent preclinical evidence indicates that trifluoperazine (TFP) inhibits treatment-induced malignant reprogramming of tumour cells, potentially helping to reduce tumour plasticity. TFP targets calmodulin, dopamine receptors, and stress-responsive proteins (nuclear protein 1, NUPR1). Through these mechanisms, TFP has been shown to reduce tumour growth, sensitise tumours to chemoradiotherapy, and prolong survival in xenograft animal models. The clinical safety profile of TFP is well known from its use as an antipsychotic, and recent preclinical evidence further indicates that TFP has low toxicity to healthy neurons and glia despite transient functional effects on dopamine receptors. This Opinion explores TFP mechanisms of action and clinical activity to assess its suitability as a repurposed therapeutic option for GBM.

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来源期刊
CiteScore
23.90
自引率
0.70%
发文量
132
审稿时长
6-12 weeks
期刊介绍: Trends in Pharmacological Sciences (TIPS) is a monthly peer-reviewed reviews journal that focuses on a wide range of topics in pharmacology, pharmacy, pharmaceutics, and toxicology. Launched in 1979, TIPS publishes concise articles discussing the latest advancements in pharmacology and therapeutics research. The journal encourages submissions that align with its core themes while also being open to articles on the biopharma regulatory landscape, science policy and regulation, and bioethics. Each issue of TIPS provides a platform for experts to share their insights and perspectives on the most exciting developments in the field. Through rigorous peer review, the journal ensures the quality and reliability of published articles. Authors are invited to contribute articles that contribute to the understanding of pharmacology and its applications in various domains. Whether it's exploring innovative drug therapies or discussing the ethical considerations of pharmaceutical research, TIPS provides a valuable resource for researchers, practitioners, and policymakers in the pharmacological sciences.
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