Reprogramming neuroblastoma by diet-enhanced polyamine depletion.

ABSTRACT: Neuroblastoma is a highly lethal childhood tumor derived from differentiation-arrested neural crest cells^1,2. Like all cancers, its growth is fueled by metabolites obtained from either circulation or local biosynthesis^3,4. Neuroblastomas depend on local polyamine biosynthesis, with the inhibitor difluoromethylornithine showing clinical activity⁵. Here we show that such inhibition can be augmented by dietary restriction of upstream amino acid substrates, leading to disruption of oncogenic protein translation, tumor differentiation, and profound survival gains in the TH-MYCN mouse model. Specifically, an arginine/proline-free diet decreases the polyamine precursor ornithine and augments tumor polyamine depletion by difluoromethylornithine. This polyami

SUBMITTER: Cherkaoui S 

PROVIDER: S-EPMC10802427 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature