ArticleNature cancer2025
Ongoing replication stress tolerance and clonal T cell responses distinguish liver and lung recurrence and outcomes in pancreatic cancer.
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Article in Nature cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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29citing papers in PubMed
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Who cites it
29 citing papers in PubMed.
- A system-level metastable model of cancer evolution: integrating replication stress, cell cycle deregulation and chromosomal instability.Annals of medicine · 2026Review
- Asynchronous Evolution of Epithelium and Stroma Differentiates Precursor Lesions from Pancreatic Cancer.Cancer discovery · 2026Article
- Heterogeneity in cancer: molecular mechanisms and therapeutic strategies.Signal transduction and targeted therapy · 2026Review
- Article
- Conserved Metastatic Cell States and Spatial Immune Microenvironment Remodeling Define Pancreatic Cancer Liver Metastases.bioRxiv : the preprint server for biology · 2026Article
- Spatiotemporal heterogeneity of recurrence and predictors after radical surgery for pancreatic ductal adenocarcinoma: a retrospective observational study.Surgical endoscopy · 2026Observational
- Pulmonary Metastases After Surgical Resection of Pancreatic Ductal Adenocarcinoma: Impact on Long-Term Survival and Perspectives on Targeted Treatments.Annals of surgical oncology · 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
- Extracellular vesicles from chemotherapy-induced senescent tumor cells reprogram hepatic phospholipid metabolism to promote pancreatic cancer liver metastasis.Journal of experimental & clinical cancer research : CR · 2026Article
- Single-cell impedance sensing on integrated circuit chip for fast tumor diagnosis.Microsystems & nanoengineering · 2026Article
- The immunobiology of pancreatic cancer metastasis: premetastatic niche formation, organ-specific immune landscapes, and therapeutic opportunities.Cancer metastasis reviews · 2026Review
- Article
- Sympathetic nerve-fibroblast crosstalk drives nerve injury, fibroblast activation, and matrix remodeling in pancreatic cancer.JCI insight · 2026Article
- High-Dimensional Protein Analysis Uncovers Distinct Immunologic and Stromal Features in Primary and Metastatic Pancreatic Ductal Adenocarcinoma.Cancer research · 2026Article
- ImmunoPheno: A Computational Framework for Data-Driven Design and Analysis of Immunophenotyping Experiments.bioRxiv : the preprint server for biology · 2026Article
- Article
- Neoadjuvant modified FOLFIRINOX plus nivolumab in borderline-resectable pancreatic ductal adenocarcinoma: a pilot phase 1 trial.Nature communications · 2026Article
- PRECOG update: an augmented resource of clinical outcome associations with gene expression for adult, pediatric, and immunotherapy cohorts.Nucleic acids research · 2026Article
- Fibroblast STAT3 Activation Drives Organ-Specific Premetastatic Niche Formation.Cancer research · 2026Article
- The Prolyl Isomerase PIN1 Affects Fibroblast Differentiation States and Cross-talk in Pancreatic Cancer.Cancer research · 2025Article
Corrections and comments
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Authors and funding
38 authors.
Jason M LinkDepartment of Molecular and Medical Genetics, Oregon Health and Science University, Portland, OR, USA. jmlink@mednet.ucla.edu.ORCID 0000-0002-6892-0431
Jennifer R EngDepartment of Molecular and Medical Genetics, Oregon Health and Science University, Portland, OR, USA.ORCID 0000-0003-1499-8417
Carl PelzBrenden-Colson Center for Pancreatic Care, Oregon Health and Science University, Portland, OR, USA.
Kevin MacPherson-HawthorneDepartment of Molecular and Medical Genetics, Oregon Health and Science University, Portland, OR, USA.
Patrick J WorthBrenden-Colson Center for Pancreatic Care, Oregon Health and Science University, Portland, OR, USA.
Shamaline SivagnanamDepartment of Cell, Development and Cancer Biology, Oregon Health and Science University, Portland, OR, USA.ORCID 0000-0001-5966-1522
Dove J KeithBrenden-Colson Center for Pancreatic Care, Oregon Health and Science University, Portland, OR, USA.ORCID 0000-0001-6104-3264
Sydney OwenBrenden-Colson Center for Pancreatic Care, Oregon Health and Science University, Portland, OR, USA.
Ellen M LangerDepartment of Molecular and Medical Genetics, Oregon Health and Science University, Portland, OR, USA.ORCID 0000-0003-0352-1859
Alison Grossblatt-WaitBrenden-Colson Center for Pancreatic Care, Oregon Health and Science University, Portland, OR, USA.ORCID 0000-0002-2838-2595
Gustavo Salgado-GarzaDepartment of Surgery, Oregon Health and Science University, Portland, OR, USA.
Allison L CreasonKnight Cancer Institute, Portland, OR, USA.ORCID 0000-0001-5724-1276
Sara ProtzekBrenden-Colson Center for Pancreatic Care, Oregon Health and Science University, Portland, OR, USA.
Julian EggerKnight Cancer Institute, Portland, OR, USA.ORCID 0000-0001-8418-0069
Hannah HollyDepartment of Molecular and Medical Genetics, Oregon Health and Science University, Portland, OR, USA.ORCID 0000-0003-2055-5372
Michael B HeskettStanford Cancer Institute, Stanford University, Palo Alto, CA, USA.
Koei ChinKnight Cancer Institute, Portland, OR, USA.ORCID 0000-0001-8061-7462
Nell KirchbergerDepartment of Cell, Development and Cancer Biology, Oregon Health and Science University, Portland, OR, USA.ORCID 0009-0003-7024-705X
Konjit BetreDepartment of Cell, Development and Cancer Biology, Oregon Health and Science University, Portland, OR, USA.
Elmar BucherDepartment of Biomedical Engineering, Oregon Health and Science University, Portland, OR, USA.
David KilburnDepartment of Biomedical Engineering, Oregon Health and Science University, Portland, OR, USA.
Zhi HuDepartment of Biomedical Engineering, Oregon Health and Science University, Portland, OR, USA.
Michael W MunksBrenden-Colson Center for Pancreatic Care, Oregon Health and Science University, Portland, OR, USA.
Isabel A EnglishDepartment of Molecular and Medical Genetics, Oregon Health and Science University, Portland, OR, USA.ORCID 0000-0002-0566-9585
Motoyuki TsudaDepartment of Molecular and Medical Genetics, Oregon Health and Science University, Portland, OR, USA.
Jeremy GoecksKnight Cancer Institute, Portland, OR, USA.ORCID 0000-0002-4583-5226
Emek DemirBrenden-Colson Center for Pancreatic Care, Oregon Health and Science University, Portland, OR, USA.
Andrew C AdeyDepartment of Molecular and Medical Genetics, Oregon Health and Science University, Portland, OR, USA.ORCID 0000-0001-7648-8717
Adel KardoshBrenden-Colson Center for Pancreatic Care, Oregon Health and Science University, Portland, OR, USA.
Charles D LopezBrenden-Colson Center for Pancreatic Care, Oregon Health and Science University, Portland, OR, USA.
Brett C SheppardBrenden-Colson Center for Pancreatic Care, Oregon Health and Science University, Portland, OR, USA.
Alex GuimaraesBrenden-Colson Center for Pancreatic Care, Oregon Health and Science University, Portland, OR, USA.
Brian BrinkerhoffBrenden-Colson Center for Pancreatic Care, Oregon Health and Science University, Portland, OR, USA.
Terry K MorganBrenden-Colson Center for Pancreatic Care, Oregon Health and Science University, Portland, OR, USA.
Gordon B MillsBrenden-Colson Center for Pancreatic Care, Oregon Health and Science University, Portland, OR, USA.ORCID 0000-0002-0144-9614
Lisa M CoussensBrenden-Colson Center for Pancreatic Care, Oregon Health and Science University, Portland, OR, USA.ORCID 0000-0003-2389-1865
Jonathan R BrodyBrenden-Colson Center for Pancreatic Care, Oregon Health and Science University, Portland, OR, USA.
Rosalie C SearsDepartment of Molecular and Medical Genetics, Oregon Health and Science University, Portland, OR, USA. searsr@ohsu.edu.ORCID 0000-0003-1558-2413
Funding
Understanding the origins of rapid recurrence of pancreatic cancer after resectionP30CA069533 · NCI · OREGON HEALTH & SCIENCE UNIVERSITY · PI Grace B Gill · 1997 to 2026
$60.5MUnderstanding the Impact of Microscale and Nanoscale Heterogeneity and ResistanceU54CA209988 · NCI · OREGON HEALTH & SCIENCE UNIVERSITY · PI GRAY, JOE W. · 2017 to 2021
$10.3MAn atlas of pancreatic tumorigenesis in the context of altered DNA repair occurring in high-risk individualsU01CA294548 · NCI · OREGON HEALTH & SCIENCE UNIVERSITY · PI BRODY, JONATHAN, FERTIG, ELANA · 2024 to 2025
$5.1MHydroxylation regulation of c-MycR01CA186241 · NCI · OREGON HEALTH & SCIENCE UNIVERSITY · PI Mu-Shui Dai, ROSALIE C SEARS · 2015 to 2026
$4.2MIntegrative bioinformatics and functional characterization of oncogenic driver aberrations in cancerU01CA217842 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI DENEEN, BENJAMIN, MILLS, GORDON B. · 2017 to 2021
$3.6MValidation of novel imaging and molecular tests for early detection of pancreatic cancer through risk-stratified community engagement programsU01CA278923 · NCI · OREGON HEALTH & SCIENCE UNIVERSITY · PI Gregory A Cote, Alexander Savio Ramos Guimaraes · 2023 to 2026
$3.3MComparative analysis between patient-derived models of pancreatic ductal adenocarcinomas and matched tumor specimensU01CA224012 · NCI · OREGON HEALTH & SCIENCE UNIVERSITY · PI BRODY, JONATHAN, COUSSENS, LISA M. · 2019 to 2023
$2.9MMechanistic maps of adaptive responses to therapeutic stress to optimize combination therapies.U01CA253472 · NCI · OREGON HEALTH & SCIENCE UNIVERSITY · PI KORKUT, ANIL, LIANG, HAN · 2021 to 2025
$2.6MThe Role of post-translational activation of Myc in pancreatic cancerR01CA196228 · NCI · OREGON HEALTH & SCIENCE UNIVERSITY · PI SEARS, ROSALIE C · 2015 to 2019
$2.0MOptimizing anti-wild-type IDH1 therapy in pancreatic cancerR01CA287672 · NCI · CASE WESTERN RESERVE UNIVERSITY · PI Jonathan Brody, Jordan M Winter · 2024 to 2026
$2.0MHigh Performance Computing and Machine Learning Infrastructure for Oregon Life SciencesS10OD034224 · OD · OREGON HEALTH & SCIENCE UNIVERSITY · PI ELLROTT, KYLE · 2023 to 2023
$2.0MTargeting HuR to improve a synthetic lethal therapy for pancreatic cancerR01CA212600 · NCI · THOMAS JEFFERSON UNIVERSITY · PI BRODY, JONATHAN · 2017 to 2021
$1.9MAmerican Association for Cancer Research (American Association for Cancer Research, Inc.) 15-90-25-BRODNCI NIH HHS P30 CA069533NCI NIH HHS R01 CA186241NCI NIH HHS R01 CA196228NCI NIH HHS R01 CA212600NCI NIH HHS R01 CA287672NCI NIH HHS R21 CA263996NCI NIH HHS U01 CA217842NCI NIH HHS U01 CA224012NCI NIH HHS U01 CA253472NCI NIH HHS U01 CA278923NCI NIH HHS U01 CA294548NCI NIH HHS U54 CA209988NIH HHS S10 OD034224U.S. Department of Defense (United States Department of Defense) PA210068U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) R01CA186241U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) R01CA196228U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) R01CA212600U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) R21CA263996U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) U01CA217842U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) U01CA224012U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) U01CA253472U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) U01CA278923U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) U54CA209988
Abstract
Patients with metastatic pancreatic ductal adenocarcinoma survive longer if disease spreads to the lung but not the liver. Here we generated overlapping, multi-omic datasets to identify molecular and cellular features that distinguish patients whose disease develops liver metastasis (liver cohort) from those whose disease develops lung metastasis without liver metastases (lung cohort). Lung cohort patients survived longer than liver cohort patients, despite sharing the same tumor subtype. We developed a primary organotropism (pORG) gene set enriched in liver cohort versus lung cohort primary tumors. We identified ongoing replication stress response pathways in high pORG/liver cohort tumors, whereas low pORG/lung cohort tumors had greater densities of lymphocytes and shared T cell clonal responses. Our study demonstrates that liver-avid pancreatic ductal adenocarcinoma is associated with tolerance to ongoing replication stress, limited tumor immunity and less-favorable outcomes, whereas low replication stress, lung-avid/liver-averse tumors are associated with active tumor immunity that may account for favorable outcomes.
Indexed as
Carcinoma, Pancreatic DuctalLiver NeoplasmsLung NeoplasmsNeoplasm Recurrence, LocalPancreatic NeoplasmsT-LymphocytesDNA ReplicationFemaleHumansMale
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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 Socratic graph.