ArticleCell reports2022
Reprogramming of nucleotide metabolism by interferon confers dependence on the replication stress response pathway in pancreatic cancer cells.
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Article in Cell reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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21citing papers in PubMed
2.2field-weighted citation impact, top 12% of its field
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Who cites it
21 citing papers in PubMed, 30 citations in OpenAlex.
- STING agonist profiling by nucleotide library defines structural determinants of cyclic dinucleotide recognition.iScience · 2026Article
- ZNF274 constrains lineage plasticity and drives intrinsic resistance to CDK7 inhibitors in pancreatic cancer.Nature communications · 2026Article
- Hierarchies of resistance to DNA damage response inhibitors: from pathway restoration to replication stress tolerance.Experimental hematology & oncology · 2026Review
- Synthetic lethality between RB-loss and E2F3 inhibition in small cell cancers targeted by pyrimidine synthesis blockade.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Targeting ATR-CHK1 and ATM-CHK2 Axes in Pancreatic Cancer-A Comprehensive Review of Literature.International journal of molecular sciences · 2026Review
- Sjögren's disease metabolome reveals biomarker signatures to characterise patients and assess disease activity.RMD open · 2026Article
- cGAS-STING signaling pathway as a therapeutic target in human diseases.Chinese medical journal · 2025Review
- Analysis of an engineered organoid model of pancreatic cancer identifies hypoxia as a contributing factor in determining transcriptional subtypes.Scientific reports · 2025Article
- ATP functions as a pathogen-associated molecular pattern to activate the E3 ubiquitin ligase RNF213.Nature communications · 2025Article
- Advances in Vaccine-Based Therapies for Pancreatic Cancer.Journal of gastrointestinal cancer · 2025Review
- Identification of fatty acid anabolism patterns to predict prognosis and immunotherapy response in gastric cancer.Discover oncology · 2025Article
- Landscape of targets within nucleoside metabolism for the modification of immune responses.Frontiers in oncology · 2025Review
- Emerging mechanisms and promising approaches in pancreatic cancer metabolism.Cell death & disease · 2024Review
- MEK Inhibition Sensitizes Pancreatic Cancer to STING Agonism by Tumor Cell-intrinsic Amplification of Type I IFN Signaling.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- SAMHD1 restricts the deoxyguanosine triphosphate pool contributing to telomere stability in telomerase-positive cells.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2023Article
- Article
- Epigenetically programmed resistance to chemo- and immuno-therapies.Advances in cancer research · 2023Article
- Dysregulation in IFN-γ signaling and response: the barricade to tumor immunotherapy.Frontiers in immunology · 2023Review
- Targeting E2F Sensitizes Prostate Cancer Cells to Drug-Induced Replication Stress by Promoting Unscheduled CDK1 Activity.Cancers · 2022Article
- Interplays of glucose metabolism and KRAS mutation in pancreatic ductal adenocarcinoma.Cell death & disease · 2022Review
Corrections and comments
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Authors and funding
23 authors at 6 institutions in 3 countries.
Evan R AbtDepartment of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, CA, USA; Ahmanson Translational Theranostics Division, University of California Los Angeles, Los Angeles, CA, USA.
Thuc M LeDepartment of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, CA, USA; Ahmanson Translational Theranostics Division, University of California Los Angeles, Los Angeles, CA, USA.
Amanda M DannDepartment of Surgery, University of California Los Angeles, Los Angeles, CA, USA.
Joseph R CapriDepartment of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, CA, USA; Ahmanson Translational Theranostics Division, University of California Los Angeles, Los Angeles, CA, USA.
Soumya PoddarDepartment of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, CA, USA; Ahmanson Translational Theranostics Division, University of California Los Angeles, Los Angeles, CA, USA.
Vincent LokDepartment of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, CA, USA; Ahmanson Translational Theranostics Division, University of California Los Angeles, Los Angeles, CA, USA.
Luyi LiDepartment of Surgery, University of California Los Angeles, Los Angeles, CA, USA.
Keke LiangDepartment of General Surgery/Pancreatic and Thyroid Surgery, Shengjing Hospital of China Medical University, Shenyang 110004, China.
Amanda L CreechDepartment of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, CA, USA; Ahmanson Translational Theranostics Division, University of California Los Angeles, Los Angeles, CA, USA.
Khalid RashidDepartment of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, CA, USA; Ahmanson Translational Theranostics Division, University of California Los Angeles, Los Angeles, CA, USA.
Woosuk KimDepartment of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, CA, USA; Ahmanson Translational Theranostics Division, University of California Los Angeles, Los Angeles, CA, USA.
Nanping WuDepartment of Surgery, University of California Los Angeles, Los Angeles, CA, USA.
Jing CuiDepartment of Pancreatic Surgery, Tongji Medical College, Huazhong University of Science and Technology, Hubei, China.
Arthur ChoDepartment of Nuclear Medicine, Yonsei University College of Medicine, Seoul 03722, South Korea.
Hailey Rose LeeDepartment of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, CA, USA; Ahmanson Translational Theranostics Division, University of California Los Angeles, Los Angeles, CA, USA.
Ethan W RosserDepartment of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, CA, USA; Ahmanson Translational Theranostics Division, University of California Los Angeles, Los Angeles, CA, USA.
Jason M LinkDepartment of Molecular and Medical Genetics, Oregon Health and Science University, Portland, OR, USA.
Johannes CzerninDepartment of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, CA, USA; Ahmanson Translational Theranostics Division, University of California Los Angeles, Los Angeles, CA, USA.
Ting-Ting WuDepartment of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, CA, USA.
Robert DamoiseauxDepartment of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, CA, USA; Jonsson Comprehensive Cancer Center, University of California Los Angeles, Los Angeles, CA, USA; California NanoSystems Institute, University of California Los Angeles, Los Angeles, CA, USA; Department of Bioengineering, Samueli School of Engineering, University of California Los Angeles, Los Angeles, CA, USA.
David W DawsonDepartment of Pathology and Laboratory Medicine, University of California Los Angeles, Los Angeles, CA, USA; David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
Timothy R DonahueDepartment of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, CA, USA; Ahmanson Translational Theranostics Division, University of California Los Angeles, Los Angeles, CA, USA; Department of Surgery, University of California Los Angeles, Los Angeles, CA, USA; Jonsson Comprehensive Cancer Center, University of California Los Angeles, Los Angeles, CA, USA; David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA. Electronic address: tdonahue@mednet.ucla.edu.
Caius G RaduDepartment of Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, CA, USA; Ahmanson Translational Theranostics Division, University of California Los Angeles, Los Angeles, CA, USA; Jonsson Comprehensive Cancer Center, University of California Los Angeles, Los Angeles, CA, USA. Electronic address: cradu@mednet.ucla.edu.
University of California, Los Angeles · USCalifornia NanoSystems Institute · USChina Medical University · CNHuazhong University of Science and Technology · CNOregon Health & Science University · USYonsei University · KR
Funding
Women's CancersP30CA016042 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Robert Damoiseaux · 1985 to 2026
$134.5MUCLA SPORE in Brain CancerP50CA211015 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Yvonne Yu-Hsuan Chen · 2017 to 2026
$25.2MUCLA Tumor Immunology Training ProgramT32CA009120 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Steven M. Dubinett, MICHAEL A TEITELL · 1985 to 2026
$10.3MLeveraging Vulnerabilities Induced by STING Activation in Pancreatic CancerR01CA250529 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DONAHUE, TIMOTHY R, RADU, CAIUS GABRIEL · 2021 to 2025
$3.1MTargeting KRAS and adenosine mediated immunosuppression in pancreatic cancerR01CA260678 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DONAHUE, TIMOTHY R, RADU, CAIUS GABRIEL · 2021 to 2025
$3.0MNCI NIH HHS P30 CA016042NCI NIH HHS P50 CA211015NCI NIH HHS R01 CA250529NCI NIH HHS R01 CA260678NCI NIH HHS T32 CA009120
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 driven by stimulator of interferon genes (STING). These results identify a cross talk between IFN, DNA replication stress response networks, and nucleotide metabolism while providing the rationale for targeted therapeutic interventions that leverage IFN signaling in tumors.
Indexed as
AdenocarcinomaAnimalsAtaxia Telangiectasia Mutated ProteinsCarcinoma, Pancreatic DuctalCell Cycle CheckpointsCell Line, TumorDNA DamageFemaleHumansInterferon Type IMaleMembrane ProteinsMiceMice, Inbred NODNucleotidesPancreatic NeoplasmsAtaxia Telangiectasia Mutated ProteinsAtr protein, mouseInterferon Type IMembrane ProteinsNucleotidesProtein Kinase InhibitorsSting1 protein, mouseSTING Proteininterferonnucleotide metabolismpancreas cancerreplication stressSTING
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