Childhood Brain Tumors: A Review of Strategies to Translate CNS Drug Delivery to Clinical Trials

Rahman, Ruman; Janowski, Miroslaw; Killick-Cole, Clare L.; Singleton, William G. B.; Campbell, Emma; Walczak, Piotr; Khatua, Soumen; Faltings, Lukas; Symons, Marc; Schneider, Julia R.; Kwan, Kevin; Boockvar, John A.; Gill, Steven S.; Miguel Oliveira, J.; Beccaria, Kevin; Carpentier, Alexandre; Canney, Michael; Pearl, Monica; Veal, Gareth J.; Meijer, Lisethe; Walker, David A.

Abstract

Brain and spinal tumors affect 1 in 1000 people by 25 years of age, and have diverse histological, biological, anatomical and dissemination characteristics. A mortality of 30–40% means the majority are cured, although two-thirds have life-long disability, linked to accumulated brain injury that is acquired prior to diagnosis, and after surgery or chemo-radiotherapy. Only four drugs have been licensed globally for brain tumors in 40 years and only one for children. Most new cancer drugs in clinical trials do not cross the blood–brain barrier (BBB). Techniques to enhance brain tumor drug delivery are explored in this review, and cover those that augment penetration of the BBB, and those that bypass the BBB. Developing appropriate delivery techniques could improve patient outcomes by ensuring efficacious drug exposure to tumors (including those that are drug-resistant), reducing systemic toxicities and targeting leptomeningeal metastases. Together, this drug delivery strategy seeks to enhance the efficacy of new drugs and enable re-evaluation of existing drugs that might have previously failed because of inadequate delivery. A literature review of repurposed drugs is reported, and a range of preclinical brain tumor models available for translational development are explored.

Citation

Rahman, R., Janowski, M., Killick-Cole, C. L., Singleton, W. G. B., Campbell, E., Walczak, P., Khatua, S., Faltings, L., Symons, M., Schneider, J. R., Kwan, K., Boockvar, J. A., Gill, S. S., Miguel Oliveira, J., Beccaria, K., Carpentier, A., Canney, M., Pearl, M., Veal, G. J., Meijer, L., & Walker, D. A. (2023). Childhood Brain Tumors: A Review of Strategies to Translate CNS Drug Delivery to Clinical Trials. Cancers, 15(3), Article 857. https://doi.org/10.3390/cancers15030857

• Journal Article Type: Article
• Acceptance Date: Jan 26, 2023
• Online Publication Date: Jan 30, 2023
• Publication Date: Jan 30, 2023
• Deposit Date: Feb 3, 2023
• Publicly Available Date: Feb 14, 2023
• Journal: Cancers
• Electronic ISSN: 2072-6694
• Publisher: MDPI
• Peer Reviewed: Peer Reviewed
• Volume: 15
• Issue: 3
• Article Number: 857
• DOI: https://doi.org/10.3390/cancers15030857
• Keywords: Cancer Research; Oncology
• Public URL: https://nottingham-repository.worktribe.com/output/16802529
• Publisher URL: https://www.mdpi.com/2072-6694/15/3/857