{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Callaghan CM"],"funding":["NIEHS NIH HHS","NCI NIH HHS","NIAMS NIH HHS","NIGMS NIH HHS"],"pagination":["933-944"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9974877"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["115(4)"],"pubmed_abstract":["<h4>Purpose</h4>Ataxia telangiectasia mutated kinase (ATM) inhibitors are potent radiosensitizers that regulate DNA damage responses and redox metabolism, but they have not been translated clinically because of the potential for excess normal tissue toxicity. Pharmacologic ascorbate (P-AscH<sup>-</sup>; intravenous administration achieving mM plasma concentrations) selectively enhances H<sub>2</sub>O<sub>2</sub>-induced oxidative stress and radiosensitization in tumors while acting as an antioxidant and mitigating radiation damage in normal tissues including the bowel. We hypothesized that P-AscH<sup>-</sup> could enhance the therapeutic index of ATM inhibitor-based chemoradiation by simultaneously enhancing the intended effects of ATM inhibitors in tumors and mitigating off-target effects"],"journal":["International journal of radiation oncology, biology, physics"],"pubmed_title":["Manipulation of Redox Metabolism Using Pharmacologic Ascorbate Opens a Therapeutic Window for Radio-Sensitization by ATM Inhibitors in Colorectal Cancer."],"pmcid":["PMC9974877"],"funding_grant_id":["T32 CA078586","P30 ES005605","P30 CA086862","K99 AR070914","T32 GM007337","P01 CA217797","P01 CA244091","R00 AR070914"],"pubmed_authors":["Allen BG","Coleman MC","George BN","Caster JM","Callaghan CM","Petronek MS","Kalen AL","Rodman SN","Goswami PC","Abukhiran IM","Van Rheeden RV","Mapuskar KA","Masaadeh A","Spitz DR"],"additional_accession":[]},"is_claimable":false,"name":"Manipulation of Redox Metabolism Using Pharmacologic Ascorbate Opens a Therapeutic Window for Radio-Sensitization by ATM Inhibitors in Colorectal Cancer.","description":"<h4>Purpose</h4>Ataxia telangiectasia mutated kinase (ATM) inhibitors are potent radiosensitizers that regulate DNA damage responses and redox metabolism, but they have not been translated clinically because of the potential for excess normal tissue toxicity. Pharmacologic ascorbate (P-AscH<sup>-</sup>; intravenous administration achieving mM plasma concentrations) selectively enhances H<sub>2</sub>O<sub>2</sub>-induced oxidative stress and radiosensitization in tumors while acting as an antioxidant and mitigating radiation damage in normal tissues including the bowel. We hypothesized that P-AscH<sup>-</sup> could enhance the therapeutic index of ATM inhibitor-based chemoradiation by simultaneously enhancing the intended effects of ATM inhibitors in tumors and mitigating off-target effects","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Mar","modification":"2026-06-03T01:17:39.1Z","creation":"2025-04-06T01:18:03.714Z"},"accession":"S-EPMC9974877","cross_references":{"pubmed":["36228747"],"doi":["10.1016/j.ijrobp.2022.10.012"]}}