Metabolic targeting of neuroblastoma, an update

Neuroblastoma is a paediatric cancer of the sympathetic nervous system that originates from the neural crest and can be categorised into stages and risk groups. Risk groups inform treatment options and high-risk cases bear a 50 % probability of relapse post-treatment remission. In neuroblastoma, MYCN amplification is the strongest predictor of unfavourable patient prognosis; circa 50 % of high-risk cases display MYCN amplification. This dismal prognosis is perhaps influenced by the MYCN-driven metabolic rewiring of these cells since the MYC family is indicated in the regulation of proliferation, cell death, metabolism, differentiation, and protein synthesis. This review aims to capture the most recent studies that investigate metabolic rewiring in MYCN-amplified and MYCN-activated cells from the perspective of alterations to glycolysis, the TCA cycle, and oxidative phosphorylation, in addition to changes to amino acid, nucleotide, and lipid metabolism that can be relevant to therapy. A better understanding of the metabolic profile of MYCN-amplified disease will facilitate the identification of effective treatment options and improve the prognosis of high-risk neuroblastoma patients. •MYCN amplification or MYCN activation in neuroblastoma, induced elevated glycolysis.•Glutamine to glutamate conversion blockage was a vulnerability in these cells.•MYCN-amplified cells showed altered metabolite abundance, including phenolic phosphate.•Glycine, serine, and threonine metabolism, fatty acid, and bile acid synthesis pathways were also altered.•Other pathways altered in MYCN-amplified NB cells were glycerolipid and purine metabolism.