{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Abt ER"],"funding":["NCI NIH HHS","National Institutes of Health","University of California, Los Angeles"],"pagination":["110236"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8893345"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["38(2)"],"pubmed_abstract":["We determine that type I interferon (IFN) response biomarkers are enriched in a subset of pancreatic ductal adenocarcinoma (PDAC) tumors; however, actionable vulnerabilities associated with IFN signaling have not been systematically defined. Integration of a phosphoproteomic analysis and a chemical genomics synergy screen reveals that IFN activates the replication stress response kinase ataxia telangiectasia and Rad3-related protein (ATR) in PDAC cells and sensitizes them to ATR inhibitors. IFN triggers cell-cycle arrest in S-phase, which is accompanied by nucleotide pool insufficiency and nucleoside efflux. In combination with IFN, ATR inhibitors induce lethal DNA damage and downregulate nucleotide biosynthesis. ATR inhibition limits the growth of PDAC tumors in which IFN signaling is dri"],"journal":["Cell reports"],"pubmed_title":["Reprogramming of nucleotide metabolism by interferon confers dependence on the replication stress response pathway in pancreatic cancer cells."],"pmcid":["PMC8893345"],"funding_grant_id":["T32CA009120","P30 CA016042","R01 CA250529","T32 CA009120","R01 1R01CA250529-01A1","P50 CA211015","R01 CA260678"],"pubmed_authors":["Dann AM","Damoiseaux R","Wu N","Poddar S","Cui J","Donahue TR","Cho A","Dawson DW","Link JM","Czernin J","Li L","Rashid K","Lee HR","Rosser EW","Kim W","Creech AL","Liang K","Le TM","Lok V","Wu TT","Abt ER","Capri JR","Radu CG"],"additional_accession":[]},"is_claimable":false,"name":"Reprogramming of nucleotide metabolism by interferon confers dependence on the replication stress response pathway in pancreatic cancer cells.","description":"We determine that type I interferon (IFN) response biomarkers are enriched in a subset of pancreatic ductal adenocarcinoma (PDAC) tumors; however, actionable vulnerabilities associated with IFN signaling have not been systematically defined. Integration of a phosphoproteomic analysis and a chemical genomics synergy screen reveals that IFN activates the replication stress response kinase ataxia telangiectasia and Rad3-related protein (ATR) in PDAC cells and sensitizes them to ATR inhibitors. IFN triggers cell-cycle arrest in S-phase, which is accompanied by nucleotide pool insufficiency and nucleoside efflux. In combination with IFN, ATR inhibitors induce lethal DNA damage and downregulate nucleotide biosynthesis. ATR inhibition limits the growth of PDAC tumors in which IFN signaling is dri","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Jan","modification":"2026-06-01T02:08:17.576Z","creation":"2024-11-19T17:27:48.21Z"},"accession":"S-EPMC8893345","cross_references":{"pubmed":["35021095"],"doi":["10.1016/j.celrep.2021.110236"]}}