Childhood Cancer

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Targeting Anti-Apoptotic Proteins in Neuroblastoma

The Johns Hopkins University School of Medicine
Heather Sweeney
Grant Type: 
POST Program Grants
Year Awarded: 
Type of Childhood Cancer: 
Project Description: 

Mentor: Dr. Jeffrey Rubens

Neuroblastoma is a common solid tumor in children accounting for 10% of new cancer diagnoses. Approximately 50% of high-risk neuroblastoma become resistant to traditional chemotherapies leading to treatment failures and death. We are in dire need of novel therapies to combat this drug resistance and improve survival. The most aggressive type of neuroblastoma has extra copies of a gene called MYCN, which causes neuroblastoma cells to be even more resistant to traditional therapies. We have previously shown that other high MYC-expressing tumors have distinct abnormalities in molecules that protect cancer cells against chemotherapy-induced cell death and contribute to high rates of therapy resistance. We aim to combat this chemotherapy resistance with a novel medication, PAC-1, that bypasses these protective molecular abnormalities to re-sensitize tumor cells to chemotherapy-induced cell death. We have previously shown that PAC-1 is well tolerated in mouse models of high MYC-expressing tumors and the medication is already starting to be tested in phase 1 clinical trials in humans. Successful completion of this grant proposal could rapidly translate into a new pediatric clinical trial aimed at improving survival in MYCN-amplified neuroblastoma.