ArticleGastroenterology2021
Targeting DNA Damage Response and Replication Stress in Pancreatic Cancer.
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Article in Gastroenterology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 papers, 4 of them syntheses that pooled it.
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96citing papers in PubMed, 4 pooled it
8.9field-weighted citation impact, top 2% of its field
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Who cites it
96 citing papers in PubMed, 4 syntheses or guidelines pooled it, 168 citations in OpenAlex.
- Organoids in translation: a bench-to-bedside framework for pancreatic cancer precision medicine.Journal of translational medicine · 2026Pooled it
- DNA damage repair mutations in pancreatic cancer- prognostic or predictive?Frontiers in oncology · 2023Pooled it
- Replication Stress: A Review of Novel Targets to Enhance Radiosensitivity-From Bench to Clinic.Frontiers in oncology · 2022Pooled it
- Homologous Recombination Deficiency in Pancreatic Cancer: A Systematic Review and Prevalence Meta-Analysis.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2021Pooled it
- Trial
- A Replication stress biomarker is associated with response to gemcitabine versus combined gemcitabine and ATR inhibitor therapy in ovarian cancer.Nature communications · 2021Trial
- ATR-dependent phosphorylation of the histone acetyltransferase HBO1 suppresses chromatin binding and promotes replication stress responses.The Journal of biological chemistry · 2026Article
- MYC serine 62 phosphorylation promotes its association with DNA double-strand breaks to facilitate repair and cell survival under genotoxic stress.Genes & development · 2026Article
- Replication origin firing capacity indicates ATR inhibitor sensitivity.Nature communications · 2026Article
- PARP2 deficiency impairs pancreatic cancer progression by promoting genomic instability and antitumor immunity.Science advances · 2026Article
- Extrapancreatic extension modifies chemotherapy benefit in resected pancreatic ductal adenocarcinoma: a population-based cohort study.Scientific reports · 2026Article
- High RMI1 expression is associated with cancer cell progression and poor prognosis in prostate cancer.Oncology reports · 2026Article
- Metabolic plasticity in pancreatic ductal adenocarcinoma progression and response to treatment.Molecular cancer · 2026Review
- Targeting ATR-CHK1 and ATM-CHK2 Axes in Pancreatic Cancer-A Comprehensive Review of Literature.International journal of molecular sciences · 2026Review
- NSMF modulates replication stress to facilitate colorectal cancer progression.Nucleic acids research · 2026Article
- Article
- Integrative Genomic and Functional Analysis Reveals NF1 Loss as a Modifier of DNA Damage and Replication Stress Responses in Ovarian Cancer.Human mutation · 2026Article
- DNA damage response inhibitors in pancreatic cancer: progress and challenges.Frontiers in oncology · 2026Review
- Pathway for the Development of ATR Inhibitors in Pediatric Malignancies: An ACCELERATE Multistakeholder Analysis.JCO precision oncology · 2026Review
- Identification of DNA Replication Stress-Related Genes as Prognostic Biomarkers for Bladder Cancer.Combinatorial chemistry & high throughput screening · 2026Article
36 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
57 authors at 20 institutions in 5 countries.
Stephan B DreyerWolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, Scotland, United Kingdom; West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, United Kingdom.
Rosie Upstill-GoddardWolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, Scotland, United Kingdom.
Viola Paulus-HockCancer Research UK Beatson Institute, Glasgow, United Kingdom.
Clara ParisDepartment of Pharmacological Faculty, Université Grenoble Alpes, Saint-Martin-d'Heres, France.
Eirini-Maria LamprakiWolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, Scotland, United Kingdom.
Eloise DrayDepartment of Biochemistry and Structural Biology, University of Texas Health San Antonio, San Antonio, Texas.
Bryan SerrelsWolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, Scotland, United Kingdom; Medical Research Council Institute of Genetics and Molecular Medicine, Edinburgh Cancer Research UK Centre, University of Edinburgh, Edinburgh, United Kingdom.
Giuseppina CaligiuriWolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, Scotland, United Kingdom.
Selma RebusWolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, Scotland, United Kingdom.
Dennis PlenkerCold Spring Harbor Laboratory, Cold Spring Harbor, New York; Lustgarten Foundation Pancreatic Cancer Research Laboratory, Cold Spring Harbor, New York.
Zachary GalluzzoCold Spring Harbor Laboratory, Cold Spring Harbor, New York; Lustgarten Foundation Pancreatic Cancer Research Laboratory, Cold Spring Harbor, New York.
Holly BruntonWolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, Scotland, United Kingdom.
Richard CunninghamWolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, Scotland, United Kingdom.
Mathias TessonCancer Research UK Beatson Institute, Glasgow, United Kingdom.
Craig NourseCancer Research UK Beatson Institute, Glasgow, United Kingdom.
Ulla-Maja BaileyWolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, Scotland, United Kingdom.
Marc JonesStratified Medicine Scotland, Queen Elizabeth University Hospital, Glasgow, United Kingdom.
Kim Moran-JonesCollege of Medicine, Veterinary, and Life Sciences, University of Glasgow, Glasgow, United Kingdom.
Derek W WrightWolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, Scotland, United Kingdom.
Fraser DuthieWolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, Scotland, United Kingdom; Department of Pathology, Queen Elizabeth University Hospital, Glasgow, United Kingdom.
Karin OienWolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, Scotland, United Kingdom; Department of Pathology, Queen Elizabeth University Hospital, Glasgow, United Kingdom; Greater Glasgow and Clyde Bio-repository, Pathology Department, Queen Elizabeth University Hospital, Glasgow, United Kingdom.
Lisa EversWolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, Scotland, United Kingdom.
Colin J McKayWolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, Scotland, United Kingdom; West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, United Kingdom.
Grant A McGregorCancer Research UK Beatson Institute, Glasgow, United Kingdom.
Aditi GulatiCancer Research UK Gene Function Laboratory and Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London, United Kingdom.
Rachel BroughCancer Research UK Gene Function Laboratory and Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London, United Kingdom.
Ilirjana BajramiCancer Research UK Gene Function Laboratory and Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London, United Kingdom.
Stephan PettittCancer Research UK Gene Function Laboratory and Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London, United Kingdom.
Michele L DziubinskiDepartment of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan.
Juliana CandidoBarts Cancer Institute, Queen Mary University of London, London, United Kingdom.
Frances BalkwillBarts Cancer Institute, Queen Mary University of London, London, United Kingdom.
Simon T BarryBioscience, Oncology, Innovative Medicines and Early Development Biotech Unit, AstraZeneca, Cambridge, United Kingdom.
Robert GrützmannDepartment of Surgery, Universitätsklinikum Erlangen, Erlangen, Germany.
Lola RahibPancreatic Cancer Action Network, Manhattan Beach, California.
Glasgow Precision Oncology Laboratory,Glasgow Precision Oncology Laboratory, Glasgow, United Kingdom.
Australian Pancreatic Cancer Genome InitiativeAustralian Pancreas Genome, Darlinghurst, Australia.
Amber JohnsThe Kinghorn Cancer Centre, Darlinghurst and Garvan Institute of Medical Research, Sydney, Australia.
Marina PajicThe Kinghorn Cancer Centre, Darlinghurst and Garvan Institute of Medical Research, Sydney, Australia.
Fieke E M FroelingLustgarten Foundation Pancreatic Cancer Research Laboratory, Cold Spring Harbor, New York; Epigenetics Unit, Department of Surgery and Cancer, Imperial College London, Hammersmith Campus, London, United Kingdom.
Phillip BeerSanger Institute, Wellcome Genome Campus, Cambridge, United Kingdom.
Elizabeth A MusgroveWolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, Scotland, United Kingdom.
Gloria M PetersenMayo Clinic, Rochester, Minnesota.
Alan AshworthDepartment of Pathology, Queen Elizabeth University Hospital, Glasgow, United Kingdom; University of California-San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California.
Margaret C FrameMedical Research Council Institute of Genetics and Molecular Medicine, Edinburgh Cancer Research UK Centre, University of Edinburgh, Edinburgh, United Kingdom.
Howard C CrawfordDepartment of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan.
Diane M SimeonePancreatic Cancer Center, Perlmutter Cancer Center, New York University Langone Health, New York, New York.
Chris LordCancer Research UK Gene Function Laboratory and Breast Cancer Now Toby Robins Research Centre, The Institute of Cancer Research, London, United Kingdom.
Debabrata MukhopadhyayDepartment of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine and Science, Jacksonville, Florida.
Christian PilarskyDepartment of Surgery, Universitätsklinikum Erlangen, Erlangen, Germany.
David A TuvesonCold Spring Harbor Laboratory, Cold Spring Harbor, New York; Lustgarten Foundation Pancreatic Cancer Research Laboratory, Cold Spring Harbor, New York.
Susanna L CookeWolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, Scotland, United Kingdom.
Nigel B JamiesonWolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, Scotland, United Kingdom; West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, United Kingdom.
Jennifer P MortonWolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, Scotland, United Kingdom; Cancer Research UK Beatson Institute, Glasgow, United Kingdom.
Owen J SansomWolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, Scotland, United Kingdom; Department of Biochemistry and Structural Biology, University of Texas Health San Antonio, San Antonio, Texas.
Peter J BaileyCancer Research UK Beatson Institute, Glasgow, United Kingdom.
Andrew V BiankinWolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, Scotland, United Kingdom; West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, United Kingdom; South Western Sydney Clinical School, Faculty of Medicine, University of New South Wales, Liverpool, Australia. Electronic address: andrew.biankin@glasgow.ac.uk.
David K ChangWolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Glasgow, Scotland, United Kingdom; West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, United Kingdom; South Western Sydney Clinical School, Faculty of Medicine, University of New South Wales, Liverpool, Australia. Electronic address: david.chang@glasgow.ac.uk.
University of Glasgow · GBGlasgow Royal Infirmary · GBCancer Research UK Scotland Institute · GBGarvan Institute of Medical Research · AUBeatson West of Scotland Cancer Centre · GBQueen Elizabeth University Hospital · GBInstitute of Cancer Research · GBUniversitätsklinikum Erlangen · DECold Spring Harbor Laboratory · USEdinburgh Cancer Research · GBThe University of Texas Health Science Center at San Antonio · USUniversity of Michigan · USPancreatic Cancer Action Network · USLustgarten Foundation · USMayo Clinic · USQueen Mary University of London · GBAstraZeneca (United Kingdom) · GBNYU Langone Health · USUCSF Helen Diller Family Comprehensive Cancer Center · USUniversité Grenoble Alpes · FR
Funding
Women's Cancer ProgramP30CA015083 · NCI · MAYO CLINIC ROCHESTER · PI AKHILESH PANDEY · 1985 to 2026
$151.3MSingle-Cell Biology Shared ResourceP30CA045508 · NCI · COLD SPRING HARBOR LABORATORY · PI John Edward Moses · 1987 to 2026
$118.9MTumor Antigens for Individual Signatures and TherapyP50CA062924 · NCI · JOHNS HOPKINS UNIVERSITY · PI JAFFEE, ELIZABETH M. · 1993 to 2022
$54.6MTissue CoreP50CA102701 · NCI · MAYO CLINIC ROCHESTER · PI MUKHOPADHYAY, DEBABRATA · 2004 to 2018
$32.7MTargeting Pancreatic Cancer Using Peptide Chemistry: From Bench to BedsideR01CA150190 · NCI · MAYO CLINIC ROCHESTER · PI MIERKE, DALE F, MUKHOPADHYAY, DEBABRATA · 2010 to 2021
$5.7MCancer Research UK 16354Cancer Research UK 21139Cancer Research UK 25714Cancer Research UK 25813Cancer Research UK 27820Cancer Research UK 29996Cancer Research UK 30322Cancer Research UK A23526Cancer Research UK C29717/A17263Cancer Research UK C29717/A18484Cancer Research UK C596/A18076Cancer Research UK C596/A20921NCI NIH HHS P30 CA015083NCI NIH HHS P30 CA045508NCI NIH HHS P50 CA062924NCI NIH HHS P50 CA102701NCI NIH HHS R01 CA150190Wellcome TrustWellcome Trust 103721/Z/14/Z
Abstract
BACKGROUND &
aimsContinuing recalcitrance to therapy cements pancreatic cancer (PC) as the most lethal malignancy, which is set to become the second leading cause of cancer death in our society. The study aim was to investigate the association between DNA damage response (DDR), replication stress, and novel therapeutic response in PC to develop a biomarker-driven therapeutic strategy targeting DDR and replication stress in PC.
methodsWe interrogated the transcriptome, genome, proteome, and functional characteristics of 61 novel PC patient-derived cell lines to define novel therapeutic strategies targeting DDR and replication stress. Validation was done in patient-derived xenografts and human PC organoids.
resultsPatient-derived cell lines faithfully recapitulate the epithelial component of pancreatic tumors, including previously described molecular subtypes. Biomarkers of DDR deficiency, including a novel signature of homologous recombination deficiency, cosegregates with response to platinum (P < .001) and PARP inhibitor therapy (P < .001) in vitro and in vivo. We generated a novel signature of replication stress that predicts response to ATR (P < .018) and WEE1 inhibitor (P < .029) treatment in both cell lines and human PC organoids. Replication stress was enriched in the squamous subtype of PC (P < .001) but was not associated with DDR deficiency.
conclusionsReplication stress and DDR deficiency are independent of each other, creating opportunities for therapy in DDR-proficient PC and after platinum therapy.
Indexed as
AdenocarcinomaBiomarkersCell Culture TechniquesCell Line, TumorDNA DamageDNA RepairDNA ReplicationHumansMolecular Targeted TherapyOrganoidsPancreatic NeoplasmsXenograft Model Antitumor AssaysBiomarkersDNA Damage ResponsePancreatic CancerPersonalized MedicineReplication Stress
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.