biostudies-literatureUnknown16(1)D'Aprile SGlioblastoma (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 dowCell death & disease336https://www.ebi.ac.uk/biostudies/studies/S-EPMC12022057biostudies-literaturePurine metabolism rewiring improves glioblastoma susceptibility to temozolomide treatment.PMC12022057Bucolo CD'Aprile SDenaro SLi Volti GMione MCTorrisi FParenti RGiallongo CAmorini AMVicario NJorgacevski JLonghitano LTibullo DDrago FBontempi VGiallongo SPotokar MZorec RfalsePurine metabolism rewiring improves glioblastoma susceptibility to temozolomide treatment.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 dow2025-01-01T00:00:00Z2025 Apr2026-06-03T01:14:26.248Z2025-07-12T03:03:53.727ZS-EPMC120220574027477610.1038/s41419-025-07667-0