MYCN Reprograms Neuroblastoma Metabolism

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