血脑屏障对脑肿瘤治疗的影响,Journal of Internal Medicine

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血脑屏障对脑肿瘤治疗的影响
Journal of Internal Medicine ( IF 9.0 ) Pub Date : 2022-01-17 , DOI: 10.1111/joim.13440
Sneha Rathi ₁ , Jessica I Griffith ₁ , Wenjuan Zhang ₁ , Wenqiu Zhang ₁ , Ju-Hee Oh ₁ , Surabhi Talele ₁ , Jann N Sarkaria ₂ , William F Elmquist ₁

Affiliation

脑肿瘤预后较差，缺乏有效的治疗方法。血脑屏障 (BBB) 是向脑肿瘤输送药物的主要障碍。在肿瘤的某些部位，BBB 可能被破坏形成血脑肿瘤屏障 (BBTB)。这种渗漏的 BBTB 可以通过对比增强磁共振成像诊断脑肿瘤；然而，这种破坏在整个肿瘤中是异质的。因此，依靠破坏的 BBTB 在脑肿瘤中实现有效药物浓度几乎没有临床成功。因此，设计药物和给药策略来克服“正常”血脑屏障以有效治疗脑肿瘤将是有益的。在这篇综述中，我们讨论了 BBB/BBTB 在脑肿瘤诊断和治疗中的作用，突出了 BBTB 的异质性。我们还讨论了改善 BBB/BBTB 药物输送以治疗原发性和转移性脑肿瘤的各种策略。认识到 BBB 代表了中枢神经系统肿瘤药物疗效的关键决定因素，这将使从基础科学更快地转化为临床应用。有必要更全面地了解阻碍原发性和转移性脑肿瘤治疗进展的因素，例如 BBB 限制的药物输送，以开发更有效的治疗方法。

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The influence of the blood–brain barrier in the treatment of brain tumours

Brain tumours have a poor prognosis and lack effective treatments. The blood–brain barrier (BBB) represents a major hurdle to drug delivery to brain tumours. In some locations in the tumour, the BBB may be disrupted to form the blood–brain tumour barrier (BBTB). This leaky BBTB enables diagnosis of brain tumours by contrast enhanced magnetic resonance imaging; however, this disruption is heterogeneous throughout the tumour. Thus, relying on the disrupted BBTB for achieving effective drug concentrations in brain tumours has met with little clinical success. Because of this, it would be beneficial to design drugs and drug delivery strategies to overcome the ‘normal’ BBB to effectively treat the brain tumours. In this review, we discuss the role of BBB/BBTB in brain tumour diagnosis and treatment highlighting the heterogeneity of the BBTB. We also discuss various strategies to improve drug delivery across the BBB/BBTB to treat both primary and metastatic brain tumours. Recognizing that the BBB represents a critical determinant of drug efficacy in central nervous system tumours will allow a more rapid translation from basic science to clinical application. A more complete understanding of the factors, such as BBB–limited drug delivery, that have hindered progress in treating both primary and metastatic brain tumours, is necessary to develop more effective therapies.

更新日期：2022-01-17

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