New developments and prospects for drug delivery in medulloblastoma
File(s)
Published version (pre-proof)
Author(s)
Bentayebi, Kaoutar
Louati, Sara
Suwan, Keittisak
Eljaoudi, Rachid
Hajitou, Amin
Type
Journal Article
Abstract
Medulloblastoma accounts for approximately 20% of all paediatric 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.
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.
Date Issued
2026-03-25
Date Acceptance
2026-03-23
Citation
Molecular Therapy Oncology, 2026
ISSN
2950-3299
Publisher
Elsevier
Journal / Book Title
Molecular Therapy Oncology
Copyright Statement
© 2026 Published by Elsevier Inc. on behalf of The American Society of Gene and Cell Therapy.
License URL
Publication Status
Published online
Article Number
201186
Date Publish Online
2026-03-25