New developments and prospects for drug delivery in medulloblastoma

Medulloblastoma accounts for approximately 20% of all pediatric brain tumors. Standard treatment typically involves a multimodal approach including surgery, radiation therapy, and chemotherapy. Despite advances in molecular classification and the development of targeted therapies, long-term survival and quality of life remain suboptimal, particularly for patients with high-risk subgroups. Although targeted therapies hold significant promise, their effective delivery to the brain remains a major challenge. The unique cerebellar microenvironment, including the blood-brain barrier, the blood-brain-tumor barrier, and the blood-cerebrospinal fluid barrier, restricts drug penetration and therapeutic efficacy. To overcome these limitations, innovative strategies are being explored to bypass or transiently modulate these barriers in a subgroup- and compartment-specific manner. These approaches include nanoparticle-based delivery systems, focused ultrasound, intrathecal administration, and rational combination therapies. Emerging platforms such as transmorphic phage/adeno-associated virus vectors and lysosomal targeting strategies are under active investigation and may further enhance therapeutic precision. This review provides a comprehensive overview of current brain-targeted drug delivery systems for medulloblastoma, highlighting barrier heterogeneity, recurrence patterns, and emerging technologies with the potential to improve therapeutic efficacy and long-term outcomes for children affected by this aggressive pediatric brain tumor.