Purine metabolism rewiring improves glioblastoma susceptibility to temozolomide treatment.

ABSTRACT: Glioblastoma (GBM) is among the deadliest cancers, characterized by poor prognosis and median survival of 12-15 months post-diagnosis. Despite aggressive therapeutic regimens, GBM treatment is still an unmet clinical need due to heterogeneity, recurrencies, and resistance. Metabolic reshaping is emerging as a critical mechanism supporting cell proliferation and sustaining chemoresistance. In this study, we explored metabolic changes induced by chemotherapy in temozolomide (TMZ)-sensitive and TMZ-resistant GBM cell lines. We found that purine levels were altered in sensitive versus resistant GBM cells, highlighting a critical role of guanosine and inosine metabolism. By using a mesenchymal-like GBM zebrafish model, we uncovered dysregulated pathways involved in purine metabolism, with a dow

SUBMITTER: D'Aprile S 

PROVIDER: S-EPMC12022057 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature