Childhood Brain Tumors: A Review of Strategies to Translate CNS Drug Delivery to Clinical Trials
Abstract
:Simple Summary
Abstract
1. Introduction
2. Overview of CNS Drug Delivery Methods
3. Augmenting Drug Passage through the BBB
3.1. Pharmacological Modulation of the BBB
3.2. Ultrasound-Induced BBB Disruption
3.3. Intra-Arterial Chemotherapy
4. Bypassing the BBB
4.1. Polymer Therapeutics for Local Delivery
4.2. Convection-Enhanced Delivery
4.2.1. Translation of the Technique from Bench to Bedside
4.2.2. Catheter Design
4.2.3. Convection-Enhanced Delivery Infusion Regimes
4.2.4. Intermittent Convection-Enhanced Delivery
4.2.5. Drug Properties Required for Convection-Enhanced Delivery
4.3. Intra-CSF or Interstitial Administration
5. Repurposing Drugs in Pediatric Neuro-Oncology
Anti-Helminthic/Psychotic/Seizure Drugs
6. Brain Tumor Models
6.1. Human-Specific In Vitro Brain Tumor Models
6.2. Rodent Models
6.2.1. Carcinogen-Induced Models of Glioma
6.2.2. Genetically Engineered Models of Brain Cancer
6.2.3. Patient-Derived Xenografts
6.3. Large Animal Models
6.3.1. Swine
6.3.2. Rabbit
6.3.3. Companion Animals
6.3.4. Non-Human Primates
7. Discussion
7.1. Choose the Tumor Type and Clinical Setting for Targeted Treatments
- Overcome primarily drug-resistant types by ensuring predictable tumor tissue levels of existing or repurposed drugs.
- Target leptomeningeal metastasis with intra-CSF delivery using existing or repurposed drugs to defer or avoid extended-field radiotherapy.
- Enhance the efficacy and reduce systemic toxicity of molecularly targeted treatments that are shown to be effective in early trials.
7.2. Identify the Preclinical Research and Development Needed for Trial Design
8. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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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.; et al. Childhood Brain Tumors: A Review of Strategies to Translate CNS Drug Delivery to Clinical Trials. Cancers 2023, 15, 857. https://doi.org/10.3390/cancers15030857
Rahman R, Janowski M, Killick-Cole CL, Singleton WGB, Campbell E, Walczak P, Khatua S, Faltings L, Symons M, Schneider JR, et al. Childhood Brain Tumors: A Review of Strategies to Translate CNS Drug Delivery to Clinical Trials. Cancers. 2023; 15(3):857. https://doi.org/10.3390/cancers15030857
Chicago/Turabian StyleRahman, Ruman, Miroslaw Janowski, Clare L. Killick-Cole, William G. B. Singleton, Emma Campbell, Piotr Walczak, Soumen Khatua, Lukas Faltings, Marc Symons, Julia R. Schneider, and et al. 2023. "Childhood Brain Tumors: A Review of Strategies to Translate CNS Drug Delivery to Clinical Trials" Cancers 15, no. 3: 857. https://doi.org/10.3390/cancers15030857
APA StyleRahman, 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., Oliveira, J. M., Beccaria, K., Carpentier, A., Canney, M., Pearl, M., Veal, G. J., ... Walker, D. A. (2023). Childhood Brain Tumors: A Review of Strategies to Translate CNS Drug Delivery to Clinical Trials. Cancers, 15(3), 857. https://doi.org/10.3390/cancers15030857