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Translational Orthotopic Models of Glioblastoma Multiforme
Published on: February 17, 2023
Opportunities in the translational pipeline for pediatric brain cancer therapies
Lindsay Rumberger Rivera1, Nora L Springer2, Katherine Bailey3
1University of Tennessee Graduate School of Medicine, Knoxville, TN, USA.
Abstract:
Primary malignant central nervous system (CNS) tumors are the leading cause of cancer-related mortality in the pediatric population. Moreover, survivors often experience significant long-term treatment-related morbidity. Challenges unique to drug delivery to the central nervous system have hampered therapeutic progress. In the past decade, significant advancements in our understanding of molecular biology, genetic alterations, and the tumor microenvironment have allowed us to improve our in vitro and laboratory animal models to better replicate diseases seen in the pediatric population. Recently, a comparative approach using naturally-occurring CNS malignancies in dogs with similar disease progression, histologic presentation, and treatment response has been proposed as an enticing model system. Given these improvements in the translational pipeline, there is an opportunity to identify and implement effective therapies more efficiently to pediatric CNS malignancy populations. IMPACT: Relevant and translational pre-clinical studies are needed to find chemotherapeutics and targeted agents that can reach therapeutic doses within tumors in children without causing systemic adverse effects. A discussion of comparative oncology is provided with the intent to foster veterinary/human oncology collaboration. While the traditional pipeline for translating medications from bench to bedside has been evolving and improving over the last decade, the advances and remaining roadblocks of this pipeline are reviewed and discussed in this article.
Insights
Pediatric central nervous system (CNS) tumors are deadly. Comparative oncology, using canine models, offers a promising approach to develop better drug delivery and treatments for children with CNS malignancies.
Area of Science:
- Oncology
- Comparative Medicine
- Translational Science
Background:
- Primary malignant central nervous system (CNS) tumors are a leading cause of cancer mortality in children.
- Survivors face significant long-term treatment-related morbidity.
- Drug delivery to the CNS presents unique challenges, hindering therapeutic progress.
Purpose of the Study:
- To review advances and challenges in the pediatric CNS tumor translational pipeline.
- To highlight the potential of comparative oncology, specifically using naturally occurring canine CNS malignancies, as a pre-clinical model.
- To foster collaboration between veterinary and human oncology.
Main Methods:
- Review of advancements in understanding CNS tumor biology, including molecular, genetic, and microenvironment factors.
- Evaluation of improved in vitro and animal models for pediatric CNS diseases.
- Discussion of the comparative approach utilizing canine CNS malignancies.
Main Results:
- Significant improvements in pre-clinical models now better replicate pediatric CNS diseases.
- Canine CNS malignancies offer a relevant model system due to similar disease progression, histology, and treatment response.
- Enhanced understanding facilitates more efficient identification of effective therapies.
Conclusions:
- Translational pre-clinical studies are crucial for identifying chemotherapeutics and targeted agents for pediatric CNS tumors.
- Comparative oncology provides a valuable platform for developing treatments with improved CNS drug delivery and reduced systemic toxicity.
- Fostering veterinary and human oncology collaboration can accelerate the development of life-saving therapies for pediatric CNS malignancies.
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