Overcoming the blood–brain tumor barrier for effective glioblastoma treatment
Abstract
Gliomas are the most common primary brain tumors. Particularly in adult patients, the vast majority of gliomas belongs to the heterogeneous group of diffuse gliomas, i.e. glial tumors characterized by diffuse infiltrative growth in the preexistent brain tissue. Unfortunately, glioblastoma, the most aggressive (WHO grade IV) diffuse glioma is also by far the most frequent one. After standard treatment, the 2-year overall survival of glioblastoma patients is approximately only 25%. Advanced knowledge in the molecular pathology underlying malignant transformation has offered new handles and better treatments for several cancer types. Unfortunately, glioblastoma multiforme (GBM) patients have not yet profited as although numerous experimental drugs have been tested in clinical trials, all failed miserably. This grim prognosis for GBM is at least partly due to the lack of successful drug delivery across the blood-brain tumor barrier (BBTB). The human brain comprises over 100 billion capillaries with a total length of 400 miles, a total surface area of 20 m(2) and a median inter-capillary distance of about 50 μm, making it the best perfused organ in the body. The BBTB encompasses existing and newly formed blood vessels that contribute to the delivery of nutrients and oxygen to the tumor and facilitate glioma cell migration to other parts of the brain. The high metabolic demands of high-grade glioma create hypoxic areas that trigger increased expression of VEGF and angiogenesis, lea…
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The existence of the blood-brain-barrier introduces a unique challenge for applying cell-based gene therapy of brain tumors.
“The existence of the blood-brain-barrier introduces a unique challenge for applying cell-based gene therapy of brain tumors (63, 64).”
From Potential Therapeutic Effects of Exosomes Packed With a miR-21-Sponge Construct in a Rat Model of Glioblastoma (2019) · cites this paper as [63]
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- Authors
- van Tellingen, O., Yetkin-Arik, B., de Gooijer, M. C., Wesseling, P., Wurdinger, T., & de Vries, H. E.
- Affiliations
- Amsterdam UMC Location Vrije Universiteit Amsterdam (NL)
- Radboud University Medical Center (NL)
- Harvard University (US)
- Venue
- Drug Resistance Updates
- Publisher
- Elsevier BV
- Published
- 2015-03
- Volume
- 19
- Pages
- 1-12
- ISSN
- 1368-7646 (ISSN-L)
- OpenAlex
- W1966720603
- Cited by
- 1,035
- References
- 4
- Citations by year
- 2026: 57 · 2025: 133 · 2024: 104 · 2023: 96 · 2022: 108 · 2021: 123 · 2020: 121 · 2019: 90 · 2018: 82 · 2017: 59 · 2016: 44 · 2015: 17
- FWCI
- 5.37
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Drug Resistance Updates (publishedVersion)
- PubMed (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- Pure Amsterdam UMC (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- Dutch Organization of Scientific Research
- European Research Council Starting Researchers Grant
- Stichting Stophersentumoren.nl
- Topics
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Health Sciences › Medicine › Genetics › Glioma Diagnosis and Treatment
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Keywords
- glioblastoma, blood-brain tumor barrier, drug delivery, blood-brain barrier disruption, bradykinin receptor antagonists
- MeSH terms
- Adult, Animals, Antineoplastic Agents, Blood-Brain Barrier, Brain Neoplasms, Glioblastoma, Humans, Prognosis, Drug Design, Drug Delivery Systems
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