Assessing Targeted Drugs for the Treatment of Pediatric Neuroblastoma

Researchers at the Center for Childhood Cancer Research (CCCR), including John M. Maris, MD, are working to identify small molecular therapies targeted to specific genetic mutations in patients with malignant neuroblastoma for evaluation in clinical trials. Newer approaches to clinical trials include developing drugs based upon the hypothesis of how they work — based on specific genetics of the tumor.

These trials are based on present understanding of mutational heterogeneity. Tumor cells from patients are being grown in the laboratory and their genetic profiles are being characterized and “bar coded.”  Experiments are model-driven: if a specific drug is shown to interact with a specific mutation, the result should be cell death.

This, however, has to be determined using tumor cells in a laboratory — the drugs cannot be administered directly to children to test the model. Strict preclinical proof-of-concept results are required prior to the start of any pediatric drug trial.  

The Pediatric Preclinical Testing Consortium is directly addressing this problem through a large NIH funded collaborative research endeavor. It covers all pediatric cancers, but the neuroblastoma section is being led by The Children’s Hospital of Philadelphia. Dozens of models from several institutions are being assessed and chosen based on the hypothesis of how drugs are supposed to work alone and in combination.

This work will subsequently inform the design of future clinical trials assessing the safety and efficacy of drugs to treat pediatric neuroblastoma and other childhood cancers.

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