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Integrating Endovascular Drug Delivery into the Therapeutic Landscape of Glioblastoma
Zahra Hasanpour-Segherlou1, Abdolreza Alikhani2, Luca Bertola3
1Department of Neurosurgery, University of Florida, Gainesville, FL 32608, USA.
Abstract:
Glioblastoma (GBM) is the most common and aggressive primary brain tumor, characterized by poor prognosis and a median survival of 12-18 months despite standard therapies such as surgery, radiation, and temozolomide chemotherapy. Its high cellular heterogeneity, along with complex mechanisms of therapy resistance, presents significant challenges for effective treatment. Conventional systemic chemotherapy is limited by the blood-brain barrier (BBB), systemic toxicity, and insufficient drug penetration into the tumor microenvironment. Emerging therapeutic strategies aim to overcome these barriers through novel chemotherapeutic agents, targeted therapies, immunotherapies, and smart drug delivery systems. Endovascular drug delivery, particularly super-selective intra-arterial cerebral infusion (SSIACI), offers a minimally invasive approach to directly target the tumor vasculature, potentially increasing drug concentration at the tumor site while reducing systemic exposure. Complementary techniques, such as MR-guided focused ultrasound, hyperosmotic disruption, and nanoparticle-based carriers, are being explored to enhance BBB penetration and retention of therapeutics within the tumor. Ongoing clinical trials and translational studies provide insights into optimizing these approaches, with future directions focused on precision medicine, biomarker-driven patient selection, and combination therapies. Integrating endovascular strategies with innovative chemotherapies and immunotherapies may transform GBM management, but further research is required to establish their efficacy and safety in clinical practice.
Insights
Glioblastoma treatment faces challenges from the blood-brain barrier and therapy resistance. Novel endovascular drug delivery methods show promise for directly targeting brain tumors and improving patient outcomes.
Area of Science:
- Neuro-oncology
- Pharmacology
- Medical Imaging
Background:
- Glioblastoma (GBM) is an aggressive brain tumor with poor prognosis, often resistant to standard treatments.
- Systemic chemotherapy for GBM is limited by the blood-brain barrier (BBB), toxicity, and poor tumor penetration.
- High cellular heterogeneity and resistance mechanisms complicate effective GBM treatment.
Purpose of the Study:
- To review emerging therapeutic strategies for glioblastoma (GBM).
- To explore the potential of endovascular drug delivery and BBB-penetrating techniques for GBM.
- To discuss future directions in precision medicine and combination therapies for GBM.
Main Methods:
- Review of current literature on glioblastoma therapies.
- Focus on endovascular approaches like super-selective intra-arterial cerebral infusion (SSIACI).
- Discussion of complementary techniques: MR-guided focused ultrasound, hyperosmotic BBB disruption, nanoparticle delivery systems.
Main Results:
- Endovascular delivery directly targets tumor vasculature, potentially increasing local drug concentration and reducing systemic exposure.
- Advanced techniques aim to enhance drug penetration across the BBB and improve retention within the tumor microenvironment.
- Ongoing trials investigate optimizing these novel approaches for glioblastoma.
Conclusions:
- Endovascular strategies combined with novel agents offer a promising avenue for improving GBM treatment efficacy.
- Precision medicine, biomarker selection, and combination therapies are key future directions.
- Further research is essential to validate the clinical efficacy and safety of these integrated approaches for glioblastoma management.
