ID #764 Building Preclinical Models for Ultra-Rare Pediatric Brain Tumors: Early Outputs of the International Rare Brain Tumor Program (IRBTR)
Dipak Poria, Jessica W Tsai, Truman Knowles, Sabine Mueller, Brian Rood, Hope Lovell, Roger Packer, Eugene Hwang, Javad Nazarian, Vijay Ramaswamy, Jessica Daggett, Alex Sickler, Aylar Babaei, Chao Di, Jo Lynne Rokita, Adriana FonsecaAbstract
Background
Rare pediatric brain tumors are difficult to study due to inherently low incidence, biological heterogeneity, and limited tissue availability. The paucity of preclinical models for these entities restricts biological insight and systematic therapeutic development.
Methods
The International Rare Brain Tumor Registry (IRBTR) established a collaborative network across North America, Europe, and South America to facilitate generation of patient-derived cell lines and patient-derived xenograft (PDX) models from primary tumor samples of ultra-rare entities. A cornerstone of the IRBTR is harmonization of standard operating procedures (SOPs) across partner institutions including specimen collection, processing, and model generation to enable reproducible workflows and scalable resources for translational research.
Results
The IRBTR model-generation network includes sites in the United States, Canada, and Switzerland, and an additional upcoming site in Colombia. To date, the IRBTR network generated fourteen patient-derived cell lines from 7 tumors, including NTRK1-fused high-grade glioma (HGG) (n = 2), MET-fused HGG (n = 3), DICER1-associated CNS sarcoma (n = 2), MN1::CXXC5 astroblastoma (n = 3), BCOR ITD (n = 1) and PRKCA-fused glioma (n = 2). In addition, an intracranial and subcutaneous PDX model has been established from a CXXC5 astroblastoma. Models are currently undergoing genomic, transcriptomic, and phenotypic characterization to confirm fidelity to the original tumors and to support mechanistic studies and therapeutic testing.
Conclusion
The IRBTR is committed to broad dissemination of these preclinical resources, including tumor models and associated multi-omics data to activate collaborative research and accelerate drug discovery for ultra-rare pediatric brain tumors. By integrating global partnerships, standardized practices, and resource sharing, IRBTR provides a sustainable framework to overcome core barriers in rare tumor research and to advance translational innovation.