Strategies to improve delivery of anticancer drugs across the blood-brain barrier to treat glioblastoma
Strategies to improve delivery of anticancer drugs across the blood-brain barrier to treat glioblastoma
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DOI：
10.1093/neuonc/nov164
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发表时间：
2016-01-01
期刊：
影响因子：
15.9
通讯作者：
Sarkaria, Jann N.
中科院分区：
文献类型：
--
作者：
Oberoi, Rajneet K.;Parrish, Karen E.;Sarkaria, Jann N.
胶质母细胞瘤（GBM）是一种致命的侵袭性脑肿瘤，对传统的放射和细胞毒性化疗具有抗性。分子靶向药物在治疗这些遗传异质性肿瘤方面有很大的希望，但却产生了令人失望的结果。这些新疗法临床失败的一个原因可能是药物无法在大块肿瘤以外的侵入性区域达到有效浓度。在这篇综述中，我们描述了血脑屏障对抗癌药物分布到GBM的肿瘤核心和浸润区域的影响。我们进一步描述了克服这些药物递送限制的潜在策略。了解限制药物递送到脑肿瘤的关键因素将指导未来开发用于增强有效药物递送到GBM的方法。
Glioblastoma (GBM) is a lethal and aggressive brain tumor that is resistant to conventional radiation and cytotoxic chemotherapies. Molecularly targeted agents hold great promise in treating these genetically heterogeneous tumors, yet have produced disappointing results. One reason for the clinical failure of these novel therapies can be the inability of the drugs to achieve effective concentrations in the invasive regions beyond the bulk tumor. In this review, we describe the influence of the blood-brain barrier on the distribution of anticancer drugs to both the tumor core and infiltrative regions of GBM. We further describe potential strategies to overcome these drug delivery limitations. Understanding the key factors that limit drug delivery into brain tumors will guide future development of approaches for enhanced delivery of effective drugs to GBM.