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Published on: April 16, 2019
Overcoming the blood brain barrier in glioblastoma: Status and future perspective
M H Ahmed1, M Canney2, A Carpentier3
1School of Cancer & Pharmaceutical Sciences, King's College London, London SE1 9NH, United Kingdom.
Abstract:
Glioblastoma is the most common primary brain malignancy in adults. Treatment of glioblastoma patients is based on neurosurgery, radiation therapy and chemotherapy. Despite this multimodal therapeutic regimen, the prognosis of glioblastoma patients is poor. Indeed, glioblastoma is very resistant to treatments due to multiple molecular and cellular mechanisms including the existence of the blood-brain barrier (BBB). The BBB consists of multiple layers surrounding brain vessels and limits drug penetration within the brain. Therefore, overcoming the BBB is a strategy to increase bioavailability and efficacy of therapeutic agents against glioblastoma cells. The development of two approaches is ongoing: i) enhancing the delivery of drugs to the brain and ii) improving the penetration of drugs into the brain. One way to enhance drug delivery to the brain is through high-dose intravenous chemotherapy, with or without bone marrow transplantation, or via intra-arterial chemotherapy, with or without disrupting the BBB through osmotic means. Conversely, improving drug penetration within the brain can be achieved through modifying either the drug itself or the BBB. Promising results in terms of safety and signals of efficacy were obtained with these approaches in early phase clinical trials. More advanced comparative clinical trials are needed to investigate the clinical benefit for glioblastoma patients.
Insights
Overcoming the blood-brain barrier (BBB) is crucial for treating glioblastoma, a resistant brain cancer. Strategies focus on enhancing drug delivery and brain penetration to improve treatment efficacy.
Area of Science:
- Neuro-oncology
- Pharmacology
- Drug Delivery
Background:
- Glioblastoma is the most common and aggressive primary brain tumor in adults.
- Current treatments (surgery, radiation, chemotherapy) offer limited efficacy due to glioblastoma's resistance and the blood-brain barrier (BBB).
- The BBB restricts drug entry into the brain, hindering effective glioblastoma treatment.
Purpose of the Study:
- To review strategies for overcoming the BBB to improve glioblastoma therapy.
- To discuss approaches enhancing drug delivery to the brain and drug penetration into brain tissue.
- To highlight the potential of these strategies in improving patient outcomes.
Main Methods:
- Review of current therapeutic strategies for glioblastoma.
- Analysis of methods to enhance drug delivery across the BBB (e.g., high-dose chemotherapy, intra-arterial delivery).
- Exploration of techniques to improve drug penetration into the brain (drug modification, BBB modification).
Main Results:
- Early clinical trials show promising safety and efficacy signals for BBB-targeting strategies.
- Approaches focus on either increasing drug concentration in the brain or improving drug diffusion.
- These methods aim to increase the bioavailability and effectiveness of anti-cancer agents.
Conclusions:
- Overcoming the BBB is a key strategy to improve glioblastoma treatment efficacy.
- Further advanced clinical trials are necessary to confirm the clinical benefits of these novel approaches.
- Targeting the BBB holds significant promise for future glioblastoma therapies.
