Researchers at Baylor College of Medicine (USA) have identified a new weak point of neuroblastoma, centered on the fact that almost 50% of children with high-risk neuroblastoma harbor extra copies of the MYCN gene (amplified MYCN), the main driver of neuroblastoma and its resistance to therapy. The study, published in Nature Communications, shows that treating neuroblastoma by directly targeting MYCN is challenging and that the present study encourages new strategies to improve survival of children with MYCN-amplified neuroblastoma by searching for metabolic vulnerabilities that could be exploited to override resistance to therapy. The authors used unbiased metabolic analysis to compare the metabolic profiles of MYCN-amplified neuroblastomas with the profiles of non-MYCN-amplified neuroblastomas. The results of their innovative approach showed that there were significant differences between tumor cell utilization of specific nutrients for tumor growth in these two groups of tumors. Thus, they found that MYCN amplification modifies tumor lipid metabolism in a way that promotes the use and biosynthesis of fatty acids, on which cells with additional copies of MYCN largely depend. Following this line of research, when they looked at what drives MYCN-amplified neuroblastomas to depend on fatty acids for growth, they found that MYCN directly regulates or increases the production of fatty acid transporter protein 2 (FATP2). By interfering with FATP2 activity, either by knocking out the gene or by blocking FATP2 action with a small molecule inhibitor, they reduced the growth of MYCN-amplified tumors.