Opportunities in the translational pipeline for pediatric brain cancer therapies.

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.