The paper details research on treating highly lethal childhood cancer neuroblastoma. The study investigates combining the existing drug difluoromethylornithine (DFMO), which inhibits polyamine synthesis, with a proline- and arginine-free diet to enhance therapeutic outcomes. Researchers found that this combined approach drastically depleted the polyamine precursor ornithine, leading to a significant survival benefit and tumor differentiation in mouse models. Mechanistically, this depletion causes specific ribosome stalling at codons ending in adenosine, preferentially suppressing the translation of cell cycle genes and promoting the translation of differentiation-associated genes, thus reprogramming the tumor proteome. Ultimately, the research proposes that targeting codon usage via metabolic stress is a viable strategy to induce therapeutic differentiation in pediatric cancers.

References:

• Cherkaoui S, Turn C S, Yuan Y, et al. Reprogramming neuroblastoma by diet-enhanced polyamine depletion[J]. Nature, 2025: 1-9.