Marizomib在脑肿瘤治疗中的应用——我们已经走了多远?

IF 3.6 3区 医学 Q2 PHARMACOLOGY & PHARMACY
Magdalena Kusaczuk, Wiktoria Monika Piskorz, Julia Domasik
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引用次数: 0

摘要

在中枢神经系统(CNS)的几种肿瘤类型中,胶质母细胞瘤(GBM)是最常见和恶性的脑肿瘤之一。迄今为止,GBM的治疗选择非常有限,导致患者预后不良。因此,人们不断寻求新的治疗方法。其中一种策略是基于蛋白酶体抑制剂(PIs)的利用。然而,尽管一些pi已被批准用于血液系统恶性肿瘤患者的治疗,但这些治疗益处不能轻易推断到脑肿瘤。这主要是由于大多数pi的血脑屏障(BBB)不渗透性,然后是它们的低脑生物利用度。Marizomib (MZB)是一种独特的,不可逆的第二代蛋白酶体抑制剂,与其他pi不同,它可以穿透血脑屏障,使其成为治疗脑肿瘤的有前途的工具。尽管MZB具有无可争议的治疗潜力,但它尚未成功地作为gbm患者的现成化疗药物引入诊所。因此,在这项工作中,我们描述了pi作为神经肿瘤药物候选者的潜力,介绍了MZB在脑肿瘤中的临床前和临床研究结果,讨论了基于MZB的治疗失败的可能原因,并描绘了MZB相关研究的未来方向。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Marizomib in the therapy of brain tumors-how far did we go and where do we stand?

Out of several types of tumors of the central nervous system (CNS), glioblastoma (GBM) represents one of the most frequent and malignant forms of brain neoplasms. To date, GBM holds very limited therapeutic options leaving patients with poor prognosis of survival. As such, novel treatment approaches are constantly quested. One of these strategies is based on the utilization of proteasome inhibitors (PIs). However, although several PIs have been approved as therapy for patients with hematological malignancies, these treatment benefits cannot not be easily extrapolated to brain tumors. This is mostly due to the blood-brain barrier (BBB) impermeability of the majority of PIs, which is then followed by their low brain bioavailability. Marizomib (MZB) is a unique, irreversible, second-generation proteasome inhibitor, which unlike other PIs can penetrate through the BBB, making it a promising therapeutic tool in brain tumors. Despite an indisputable therapeutic potential of MZB, it has yet failed to be successfully introduced to the clinics as a ready-to-use chemotherapy for GBM-suffering patients. Therefore, in this work we describe the potential of PIs as candidates for neuro-oncological drugs, present results of preclinical and clinical investigations concerning MZB in brain tumors, discuss possible reasons of failure of MZB-based therapies and delineate future directions of MZB-related studies.

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来源期刊
Pharmacological Reports
Pharmacological Reports 医学-药学
CiteScore
8.40
自引率
0.00%
发文量
91
审稿时长
6 months
期刊介绍: Pharmacological Reports publishes articles concerning all aspects of pharmacology, dealing with the action of drugs at a cellular and molecular level, and papers on the relationship between molecular structure and biological activity as well as reports on compounds with well-defined chemical structures. Pharmacological Reports is an open forum to disseminate recent developments in: pharmacology, behavioural brain research, evidence-based complementary biochemical pharmacology, medicinal chemistry and biochemistry, drug discovery, neuro-psychopharmacology and biological psychiatry, neuroscience and neuropharmacology, cellular and molecular neuroscience, molecular biology, cell biology, toxicology. Studies of plant extracts are not suitable for Pharmacological Reports.
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