External Institution: St. Jude Children’s Research Hospital

External Collaborator: Elizabeth Stewart, MD

FDA participants: Martha Donoghue, MD; Sonia Singh, MD

Project Start Date: October 2021

Regulatory Science Challenge

Pediatric solid tumors represent a diverse group of cancers which can be difficult to treat, particularly for patients who have disease that has returned following treatment. The lack of effective laboratory tests to screen drugs for the treatment of these rare childhood cancers before they are evaluated in the clinic is a major obstacle to pediatric cancer research. There is limited availability of patient tumor samples and a lack of model systems which can adequately reflect the complexity of cancers that occur in children. Furthermore, the current pediatric tumor model systems available for testing lack major components of the tumor microenvironment (TME) which may influence the responsiveness or resistance to chemotherapeutic agents. Overcoming this challenge is critical to assess the safety, efficacy, quality, and performance of drugs for the treatment of children with cancer. 

Project Description and Goals

To improve our ability to evaluate newer agents that may benefit pediatric patients with cancer, we aim to develop 200 new orthotopic patient-derived tumor models (O-PDX) with matched patient-specific induced pluripotent stem cells (iPSCs) that can be reprogrammed for modeling of the TME. Samples of the primary tumor in pediatric patients with solid tumors will be collected at the time of initial diagnosis, tumor resection, or disease recurrence and implanted into a relevant location in an immunocompromised mouse. In addition, skin biopsies will be collected at the same time from each patient to grow skin fibroblasts that can be reprogrammed into iPSCs. Those iPSCs can then be converted into the normal components of the TME such as macrophages, natural killer (NK) cells, or vascular endothelial cells and combined with the tumor cells both in the laboratory (in vitro) and in animal models (in vivo).

We intend to use these model systems of combined tumor cells with the normal cells of the TME to test new drug combinations to help identify which drugs have the most potential to treat pediatric cancers and should be prioritized for study in pediatric clinical trials.  In addition, all tumor models systems, characterization data, and matched iPSCs will be made freely available to the scientific community through the Childhood Scientific Tumor Network.

Further Information

• OCE Scientific Collaborative
• FDA Broad Agency Announcement: Frequently Asked Questions for Oncology Researchers
• OCE-Funded Active Extramural Research Projects