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Although elevated reactive oxygen species support tumor progression, glioblastoma relies on robust antioxidant systems including the\n                    <jats:italic>SLC7A11<\/jats:italic>\n                    \u2010\n                    <jats:italic>GPX4<\/jats:italic>\n                    axis to buffer oxidative stress, creating a targetable vulnerability. Here, we investigate\n                    <jats:italic>Rosasina<\/jats:italic>\n                    , a sodium\u2010chlorite (NaClO\n                    <jats:sub>2<\/jats:sub>\n                    )\u2010derived, redox\u2010active small molecule, as a selective pro\u2010oxidant strategy to disrupt glioblastoma antioxidant resilience and induce ferroptotic cell death.\n                    <jats:italic>Rosasina<\/jats:italic>\n                    preferentially increased intracellular ROS in glioblastoma cells relative to normal human astrocytes, with hydrogen peroxide representing the predominant ROS species. This oxidative shift was accompanied by expansion of the labile iron pool and enhanced lipid peroxidation. In orthotopic glioblastoma models,\n                    <jats:italic>Rosasina<\/jats:italic>\n                    was well tolerated, significantly reduced tumor growth, prolonged survival, and exhibited no evidence of treatment\u2010related systemic toxicity, with preserved histological integrity of major organs. Mechanistically,\n                    <jats:italic>Rosasina<\/jats:italic>\n                    induces a coordinated pro\u2010ferroptotic transcriptional program, characterized by upregulation of iron uptake and lipid peroxidation pathways (\n                    <jats:italic>NCOA4, NOX5, ACSL4, TFRC<\/jats:italic>\n                    ), alongside suppression of antioxidant defenses, including\n                    <jats:italic>GPX4, GCH1, SCD1<\/jats:italic>\n                    , and\n                    <jats:italic>SLC7A11<\/jats:italic>\n                    . In addition to its tumor\u2010intrinsic effects,\n                    <jats:italic>Rosasina<\/jats:italic>\n                    promoted macrophage polarization toward an anti\u2010tumor, pro\u2010inflammatory M1\u2010like phenotype without compromising macrophage viability, suggesting a potential role in tumor immune microenvironment reprogramming. Collectively, these findings establish\n                    <jats:italic>Rosasina<\/jats:italic>\n                    as a redox\u2010directed therapeutic that selectively exploits the oxidative vulnerabilities of glioblastoma to induce ferroptosis simultaneously promoting antitumor immune reprogramming. This study provides a mechanistic framework for the development of redox\u2010targeted therapies for glioblastoma.\n                  <\/jats:p>","DOI":"10.1002\/smmd.70058","type":"journal-article","created":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T04:21:59Z","timestamp":1791519719000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Selective Pro\u2010Oxidant Drives Redox Reprogramming to Induce Ferroptosis and Immune Remodeling in Glioblastoma"],"prefix":"10.1002","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9938-7043","authenticated-orcid":false,"given":"Shilpi","family":"Singh","sequence":"first","affiliation":[{"name":"Department of Neurosurgery University of Minnesota  Minneapolis Minnesota 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