The Research to Accelerate Cures and Equity (RACE) for Children Act, approved by the United States Congress in 2017, now mandates that new oncology drugs be tested in children if their molecular targets are relevant to pediatric diseases, before US Food and Drug Administration (FDA) approval. This is crucial because most cancer drugs are developed for adults and may not work for childhood cancers, where repurposing adult drugs has been the main option for children who have exhausted established treatments.
However, Stefan Pfister, a pediatric oncologist at the Hopp Children’s Cancer Center Heidelberg (KiTZ), Germany, notes the challenge: "There will never be enough patients, fortunately, to run paediatric clinical trials for all new oncology drugs." The solution lies in preclinical testing, and researchers at Charles River Laboratories, within the Innovative Therapies for Children with Cancer Paediatric Preclinical Proof-of-concept Platform (ITCC-P4), have co-established a system to prioritize drugs for pediatric testing and accelerate their path to clinical use.
The Role of Pediatric PDX Models
Pediatric tumors differ significantly from adult tumors, often with different genetic drivers. Julia Schueler, therapeutic area lead in oncology at Charles River, emphasizes the need for a targeted preclinical testing system: "Especially in a paediatric field, where all cancer types are rare diseases, you need a model for exactly that disease." The new system relies primarily on patient-derived xenograft (PDX) models, created by grafting tissue from pediatric tumors into immunocompromised mice, preserving the original tumor's heterogeneity. "PDX models have the advantage of resembling the patient cohort of the disease," Schueler explains.
Charles River is part of the ITCC-P4 consortium, which began in 2017 as a non-profit organization supporting drug developers in preclinical testing for potential pediatric targets. According to Schueler, "The driver behind the consortium is that this is something you cannot do on your own. It’s simply not possible."
The consortium offers 200 well-characterized PDX models, with another 200 in development. Pfister, co-founder of the ITCC-P4, adds, "We are also establishing genetic models that can be transplanted to immunocompetent mice," allowing expansion into preclinical testing for immuno-oncology drugs.
Drug developers can access expert support from ITCC-P4’s academic network and Charles River’s preclinical drug development experience. Preclinical results will be reported to regulatory authorities, helping prioritize drugs for clinical trials, reduce approval times, and meet regulatory responsibilities. Ultimately, this collaborative effort aims to provide more treatment options for children with cancer. Pfister concludes, "This is a huge opportunity to get more innovation to our patients."
