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解决血脑屏障异质性：向脑肿瘤给药的新范式。

Addressing BBB Heterogeneity: A New Paradigm for Drug Delivery to Brain Tumors.

作者信息

Griffith Jessica I, Rathi Sneha, Zhang Wenqiu, Zhang Wenjuan, Drewes Lester R, Sarkaria Jann N, Elmquist William F

机构信息

Department of Pharmaceutics, University of Minnesota, Minneapolis, MN 55455, USA.

Department of Biomedical Sciences, University of Minnesota Medical School-Duluth, Duluth, MN 55812, USA.

出版信息

Pharmaceutics. 2020 Dec 11;12(12):1205. doi: 10.3390/pharmaceutics12121205.

DOI:10.3390/pharmaceutics12121205
PMID:33322488
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7763839/
Abstract

Effective treatments for brain tumors remain one of the most urgent and unmet needs in modern oncology. This is due not only to the presence of the neurovascular unit/blood-brain barrier (NVU/BBB) but also to the heterogeneity of barrier alteration in the case of brain tumors, which results in what is referred to as the blood-tumor barrier (BTB). Herein, we discuss this heterogeneity, how it contributes to the failure of novel pharmaceutical treatment strategies, and why a "whole brain" approach to the treatment of brain tumors might be beneficial. We discuss various methods by which these obstacles might be overcome and assess how these strategies are progressing in the clinic. We believe that by approaching brain tumor treatment from this perspective, a new paradigm for drug delivery to brain tumors might be established.

摘要

脑肿瘤的有效治疗方法仍然是现代肿瘤学中最紧迫且未得到满足的需求之一。这不仅是因为神经血管单元/血脑屏障（NVU/BBB）的存在，还因为脑肿瘤情况下屏障改变的异质性，这导致了所谓的血瘤屏障（BTB）。在此，我们讨论这种异质性、它如何导致新型药物治疗策略的失败，以及为什么采用“全脑”方法治疗脑肿瘤可能有益。我们讨论了克服这些障碍的各种方法，并评估这些策略在临床上的进展情况。我们相信，从这个角度来探讨脑肿瘤治疗，可能会建立一种向脑肿瘤给药的新范式。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/daa0/7763839/8324be2ab5e7/pharmaceutics-12-01205-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/daa0/7763839/84c9b4433fd5/pharmaceutics-12-01205-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/daa0/7763839/bc800d9ecc1e/pharmaceutics-12-01205-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/daa0/7763839/4c7106c3782e/pharmaceutics-12-01205-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/daa0/7763839/bc6936318915/pharmaceutics-12-01205-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/daa0/7763839/8324be2ab5e7/pharmaceutics-12-01205-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/daa0/7763839/84c9b4433fd5/pharmaceutics-12-01205-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/daa0/7763839/bc800d9ecc1e/pharmaceutics-12-01205-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/daa0/7763839/4c7106c3782e/pharmaceutics-12-01205-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/daa0/7763839/bc6936318915/pharmaceutics-12-01205-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/daa0/7763839/8324be2ab5e7/pharmaceutics-12-01205-g005.jpg

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本文引用的文献

[1]
PET, image-guided HDAC inhibition of pediatric diffuse midline glioma improves survival in murine models.

Sci Adv. 2020-7

[2]
New Insights into the Dysfunctions of Pericytes and Neurovascular Units in Neurodegenerative Diseases.

Neurosci Bull. 2020-12

[3]
Delivery of drugs, proteins, and nucleic acids using inorganic nanoparticles.

Adv Drug Deliv Rev. 2020

[4]
Intrathecal administration of anti-HER2 treatment for the treatment of meningeal carcinomatosis in breast cancer: A metanalysis with meta-regression.

Cancer Treat Rev. 2020-6-3

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Cerebrospinal fluid circulating tumor cells as a quantifiable measurement of leptomeningeal metastases in patients with HER2 positive cancer.

J Neurooncol. 2020-7

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Brain delivery of therapeutic proteins using an Fc fragment blood-brain barrier transport vehicle in mice and monkeys.

Sci Transl Med. 2020-5-27

[7]
Brain delivery and activity of a lysosomal enzyme using a blood-brain barrier transport vehicle in mice.

Sci Transl Med. 2020-5-27

[8]
HER2 antibody-drug conjugate controls growth of breast cancer brain metastases in hematogenous xenograft models, with heterogeneous blood-tumor barrier penetration unlinked to a passive marker.

Neuro Oncol. 2020-11-26

[9]
Synergistic drug combinations for a precision medicine approach to interstitial glioblastoma therapy.

J Control Release. 2020-7-10

[10]
Comparison of Absolute Protein Abundances of Transporters and Receptors among Blood-Brain Barriers at Different Cerebral Regions and the Blood-Spinal Cord Barrier in Humans and Rats.

Mol Pharm. 2020-6-1

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