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Targeting Protein Translation to Antagonize MYC-driven Neuroblastoma

Children’s Hospital of Philadelphia
Andrea Flynn, MD
Grant Type: 
Young Investigator Grants
Year Awarded: 
Type of Childhood Cancer: 
Project Description: 


Each year in the US over 700 children are diagnosed with neuroblastoma, a tumor responsible for 15% of all childhood cancer deaths. Neuroblastoma arises from the developing nervous tissue (outside the brain), and usually behaves aggressively. Treatment currently includes intensive therapy, yet only about 50% of children with high-risk disease survive long term. Difluoromethylornithine (DFMO) is a drug that is FDA-approved to treat an infection called "Trypanosomiasis". DFMO blocks an enzyme (Odc) needed to make chemicals called polyamines, which have been found to be necessary for human cells to grow quickly, especially cancer cells. Tumors in which a cancer gene called MYC has been turned on are particularly dependent on polyamines. 

Project Goal:

We and others have shown that DFMO has strong activity against neuroblastoma (which often has its MYC gene turned on), so we aim to "re-purpose" DFMO as a novel neuroblastoma drug. Here we will explore which types of genetic changes make neuroblastoma cells vulnerable to DFMO. We found that some neuroblastomas have turned on their ODC1 gene (which makes the enzyme that DFMO targets) in addition to their MYC gene. We can test tumors to see which ones DFMO works best against. We also need to understand what exactly DFMO does besides depleting the tumor of polyamines. Our work so far shows that DFMO treatment poisons the ability of these cells to make proteins, and we will characterize further. With this knowledge we will be better able to predict which children with neuroblastoma may respond best to DFMO.

Co-funded by: 
Cure4Cam Childhood Cancer Foundation