Reprogramming neuroblastoma by diet-enhanced polyamine depletion.

- Extra-tumoral conversion of arginine feeds tumor ornithine via uptake from circulation in MYCN-neuroblastoma.- A proline and arginine free diet enhances pharmacological polyamine depletion via reduced ornithine substrate availability.- Polyamine depletion disrupts oncogenic translation to induce a pro-differentiation proteome causing neuroblast differentiation and prolonged survival in the TH-MYCN mouse model.- Genes of specific cellular programs have evolved codon usage preferences that enable coherent translational rewiring in response to metabolic stress, such as polyamine depletion.