Integrating Endovascular Drug Delivery into the Therapeutic Landscape of Glioblastoma

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.