Developments in Blood-Brain Barrier Penetrance and Drug Repurposing for Improved Treatment of Glioblastoma.
Developments in Blood-Brain Barrier Penetrance and Drug Repurposing for Improved Treatment of Glioblastoma.
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DOI：
10.3389/fonc.2018.00462
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发表时间：
2018
影响因子：
4.7
通讯作者：
Tran NL
中科院分区：
文献类型：
--
作者：
Harder BG;Blomquist MR;Wang J;Kim AJ;Woodworth GF;Winkles JA;Loftus JC;Tran NL
胶质母细胞瘤（GBM）是最常见、致命和难以治疗的成人脑肿瘤之一。手术切除肿瘤，然后放疗（RT）和替莫唑胺（TMZ）管理，是目前的治疗方式，但这种方案只能适度提高患者的总体生存率。细胞侵入周围健康的脑组织会阻碍完全的手术切除，并使旨在保留神经功能的治疗策略复杂化。尽管我们为增加对GBM的了解做出了重大努力，但自2005年以来，治疗进展相对较少，设计用于有效治疗对治疗有抗性的复发性肿瘤的治疗方法甚至更少。因此，虽然迫切需要将新的治疗方法引入临床，但新出现的证据表明，GBM位置和生物学独特的关键特征，即血脑屏障（BBB）和肿瘤内分子异质性，分别是有效治疗的关键未解决障碍。值得注意的是，GBM组织的基因组分析已经鉴定出许多控制细胞生长、侵袭和存活信号传导途径的基因改变;然而，显示出针对由这些基因改变介导的信号传导途径的临床前潜力的药物不能在肿瘤部位达到有效浓度。因此，识别血脑屏障穿透药物和利用新的和更安全的方法来增强药物递送通过血脑屏障已成为深入研究的领域。重新利用和组合FDA批准的药物与渗透到中枢神经系统（CNS）的证据也看到了新的兴趣，用于治疗原发性和复发性GBM。在这篇综述中，我们讨论了新兴的方法，以战略性地提高药物输送到GBM和重新利用目前批准的和以前研究的药物使用合理的组合策略。
Glioblastoma (GBM) is one of the most common, deadly, and difficult-to-treat adult brain tumors. Surgical removal of the tumor, followed by radiotherapy (RT) and temozolomide (TMZ) administration, is the current treatment modality, but this regimen only modestly improves overall patient survival. Invasion of cells into the surrounding healthy brain tissue prevents complete surgical resection and complicates treatment strategies with the goal of preserving neurological function. Despite significant efforts to increase our understanding of GBM, there have been relatively few therapeutic advances since 2005 and even fewer treatments designed to effectively treat recurrent tumors that are resistant to therapy. Thus, while there is a pressing need to move new treatments into the clinic, emerging evidence suggests that key features unique to GBM location and biology, the blood-brain barrier (BBB) and intratumoral molecular heterogeneity, respectively, stand as critical unresolved hurdles to effective therapy. Notably, genomic analyses of GBM tissues has led to the identification of numerous gene alterations that govern cell growth, invasion and survival signaling pathways; however, the drugs that show pre-clinical potential against signaling pathways mediated by these gene alterations cannot achieve effective concentrations at the tumor site. As a result, identifying BBB-penetrating drugs and utilizing new and safer methods to enhance drug delivery past the BBB has become an area of intensive research. Repurposing and combining FDA-approved drugs with evidence of penetration into the central nervous system (CNS) has also seen new interest for the treatment of both primary and recurrent GBM. In this review, we discuss emerging methods to strategically enhance drug delivery to GBM and repurpose currently-approved and previously-studied drugs using rational combination strategies.
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影响因子：
11.2
作者：
Hu YL;DeLay M;Jahangiri A;Molinaro AM;Rose SD;Carbonell WS;Aghi MK
通讯作者：
Aghi MK
DOI：
10.4161/cc.8.20.9701
发表时间：
2009-10-15
期刊：
Cell cycle (Georgetown, Tex.)
影响因子：
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作者：
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DOI：
10.1016/j.neo.2018.05.001
发表时间：
2018-07
期刊：
Neoplasia (New York, N.Y.)
影响因子：
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作者：
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影响因子：
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作者：
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作者：
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