Targeting Abnormal Metabolism in Neuroblastoma

Background:
We have demonstrated that inhibitors of glutamine metabolism such as DON, acivicin, and Compound 968 effectively kill medulloblastoma cells and prevent the growth of MYC-driven medulloblastoma orthotopic xenografts. NMYC amplified neuroblastoma also shows increased glutamine metabolism. We do not know if inhibitors of glutamine metabolism will effectively kill neuroblastoma cells.

Project Goal:

We hypothesize that neuroblastoma, like medulloblastoma, will be sensitive to drugs targeting glutamine metabolism. We will test this hypothesis by treating neuroblastoma cells with DON, acivicin, and Compound 968 and measuring cell growth, proliferation, and apoptosis. Using western blot and qPCR, we will interrogate enzymes and transporters involved in glutamine metabolism, with the goal of identifying a biomarker that would predict sensitivity to glutamine metabolic inhibitors. Since the pediatric phase I doses of DON and acivicin are already known, proving these compounds are active in preclinical studies may lead to clinical trials of these agents in poor prognosis NMYC and MYC-driven pediatric malignancies.