<scp>ODC</scp> ‐Driven Polyamines Synthesis Sustains the Self‐Renewal of Glioblastoma Stem Cells and Drives Tumor Aggressiveness

Glioblastoma stem cells (GSCs) are crucial drivers of tumor progression and therapeutic resistance in glioblastoma multiforme (GBM), yet the molecular mechanisms maintaining their self-renewal remain incompletely understood. Here, we identify a critical role for polyamine metabolism in GSCs maintenance. We show that GSCs exhibit elevated polyamine levels compared to non-stem tumor cells, attributed to enhanced ornithine decarboxylase (ODC) expression. High ODC expression correlates with poor patient prognosis in GBM. Genetic and pharmacologic targeting of ODC attenuated GSCs self-renewal and tumorigenicity. Our findings reveal a previously unrecognized metabolic dependency of GSCs on polyamine synthesis, and ODC may be a potential therapeutic target in GBM.