NCI has funded five research teams to participate in its Pediatric Preclinical Testing Consortium.
The consortium is designed to focus on preclinical models in order to help prioritize agents for entry into clinical trials.
“Effective prioritization of potential drug candidates is critical,” Malcolm Smith, associate branch chief of Pediatrics in NCI’s Cancer Therapy Evaluation Program, said in a statement. “There is a large universe of anticancer agents being developed for adult cancers, but because of the relatively small number of children with specific cancers, only a limited number of these agents can be studied in pediatric clinical trials.”
The five research teams were selected to conduct preclinical testing for childhood cancers based on their experience and on the preclinical models that they have previously developed. The principal investigators of each research team are:
- Richard Gorlick, Albert Einstein College of Medicine: Osteosarcoma
- Peter Houghton, Greehey Children’s Cancer Research Institute. (Sarcoma and renal cancers.)
- Xiao-Nan Li, Baylor College of Medicine. (Brain cancers.)
- John Maris, Children’s Hospital of Philadelphia. (Neuroblastoma.)
- Richard Lock, Children’s Cancer Institute of Sydney, Australia. (Leukemia.)
“The primary rationale for this consortium is the fact that there are very few new drugs for pediatric cancer, and many of those drugs that have been introduced have been dependent on the results of clinical trials in adults,” CHOP’s Maris said in a statement. “Before testing a drug in children, we need a scientific basis for using it, based on deep understanding of the biology involved, and supported by promising results in cell and animal models. These preclinical findings will provide stronger evidence for us to engage proactively with drug companies who could partner in developing these drugs.”
The consortium follows on the work of the Pediatric Preclinical Testing Program (PPTP), a decade-long initiative in which NCI worked with more than 50 pharmaceutical companies to test novel agents in PPTP-provided preclinical models.
One of the most important findings from the PPTP was that many agents that have shown efficacy against adult cancers had limited activity in pediatric preclinical models.
Some investigational drugs did show substantial activity in several models, however, including the MEK inhibitor selumetinib in gliomas with mutations in the BRAF gene and the PARP inhibitor talazoparib (in combination with low-dose temozolomide) for Ewing sarcoma. Both of these agents are now being tested in ongoing pediatric clinical trials.
The PPTP and other research teams have also shown that preclinical testing, when combined with knowledge about the relative drug exposures that can be tolerated by mice and humans, “provides powerful insight into the likely clinical utility of experimental agents,” Smith said in a statement.
Research Triangle Institute is the coordinating center for the PPTC.
