ABSTRACT
Despite current aggressive regimens, the majority of patients with MYCN amplification die due to drug-resistant disease, and further intensification ofchemotherapy will not significantly improve this outcome. We propose an entirely novel strategy to oppose MYCN oncogenic function in NB: by blockingthe metabolic reprogramming driven by MYCN. Based on our data and the recent literature, our guiding hypotheses are that: a) lipid metabolism is requiredfor NB tumorigenesis, and b) targeting MYCN-driven lipogenesis will effectively block NB tumor growth. We have demonstrated that lipid metabolism is aselective metabolic dependency of MYCN-driven tumors. MYCN drives both fatty acid (FA) synthesis and FA uptake to maintain NB cell survival. TargetingFA uptake effectively blocks NB in vivo tumor growth.