The ITCC-P4 PDX Platform Enables Preclinical Testing of Pediatric Cancers.

Cancer is the leading cause of disease-related deaths among children in high-income countries. Tumor heterogeneity and the lack of mechanism of action-based therapeutic options are key challenges to overcome to improve the survival of pediatric patients with cancer. To address these challenges, we formed the European Union-Innovative Medicines Initiative 2 (EU-IMI2) funded public-private partnership "Innovative Therapies for Children with Cancer Paediatric Preclinical Proof-of-Concept Platform" (ITCC-P4), which built a large repertoire of patient-derived xenograft (PDX) models representing all major high-risk solid pediatric cancer types for in vivo drug testing. A total of 353 PDX models were established from diagnostic and relapsed pediatric cancers and molecularly characterized, together with matched germline/tumor samples. Serial PDX models were also established, spanning diagnostic/posttreatment, primary/relapse, and metastasis-derived pairs. Proof-of-concept in vivo drug screening data in neuroblastoma and rhabdomyosarcoma models identified potential predictive biomarkers for targeted therapy. Molecular data from the PDX models, accessible at https://r2platform.com/itcc-p4, allowed the selection of models for preclinical testing based on oncogenic drivers and/or potential biomarkers. Operated by a nonprofit entity, this sustainable platform aids academic and industrial researchers in developing and prioritizing innovative therapies for pediatric cancer. SIGNIFICANCE: The ITCC-P4 platform comprises models of diagnostic/refractory/relapsed pediatric cancers that mimic patient tumors and feature intertumoral heterogeneity, providing a resource of molecularly characterized patient-derived models for in vivo testing.