Assessment of strategies for a blood-brain barrier opening in glioblastoma
(2024)
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- Abstract
- Glioblastoma (GB) is the most common and aggressive brain cancer. Despite an aggressive therapeutic procedure, prognosis remains poor with high recurrence rates. BBB is one of the main factors behind treatment resistance. While it has been shown to be disrupted in GB, an intact BBB is still found peritumorally. This heterogeneous disruption leads to a poor drug delivery to the tumor site, especially to the infiltrative tumor cells in the tumor margins at the origins of recurrence. Strategies to open the BBB have been described as promising to enhance delivery in the tumor margins. The aim of this Ph.D. thesis was to evaluate those strategies in GB including osmotic shock, irradiation and tumor vessel normalization. BBB opening was assessed via imaging (DCE-MRI) and histology (Evans blue). We demonstrated that the use of a hypertonic mannitol solution to induce osmotic shock and low-dose irradiation appear to be promising methods to enhance the delivery of compounds to tumor margins in glioblastoma, while the normalization effect using an anti-angiogenic agent needs to be further investigated to be able to state a potential efficacy of its use in the treatment of glioblastoma.
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Conq, J. (2024). Assessment of strategies for a blood-brain barrier opening in glioblastoma. https://hdl.handle.net/2078.5/243025