ArticleCell2021
Microenvironment drives cell state, plasticity, and drug response in pancreatic cancer.
Open access · greenAbstract read
In one paragraph
Article in Cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 375 papers, 2 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
375citing papers in PubMed, 2 pooled it
31.8field-weighted citation impact, top 1% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
375 citing papers in PubMed, 2 syntheses or guidelines pooled it, 556 citations in OpenAlex.
- Organoids in translation: a bench-to-bedside framework for pancreatic cancer precision medicine.Journal of translational medicine · 2026Pooled it
- Research trends and knowledge structure of pancreatic cancer and type 2 diabetes mellitus research: a two-decade CiteSpace analysis.Frontiers in endocrinology · 2026Pooled it
- Gemcitabine and nab-paclitaxel with or without the VDR agonist paricalcitol for metastatic pancreatic cancer: a randomized, multiarm, run-in phase trial.Nature cancer · 2026Trial
- Trial
- Open-Label, Phase II Trial of Extracellular Regulated Kinase Inhibition Alone and in Combination With Autophagy Inhibition in Patients With Metastatic Pancreatic Cancer.JCO precision oncology · 2025Trial
- Cancers modulate processing and presentation of p53 neoantigens to evade T cell detection.Immunity · 2026Article
- Clonal heterogeneity in human pancreatic ductal adenocarcinoma and its impact on tumor progression.Nature genetics · 2026Article
- Cell plasticity in cancer and therapy resistance.Experimental & molecular medicine · 2026Review
- Tumor cell-intrinsic stress states drive sensitivity to CAR T cell therapy in pancreatic cancer.Science advances · 2026Article
- Basal Marker ΔNp63α Is Enriched in Pancreatic Cancer Metastases but Not in Primary Tumors Post-Chemotherapy.Cancer medicine · 2026Article
- Article
- Developmental and MAPK-responsive transcription factors regulate distinct malignant cell states and associated genetic dependencies in pancreatic cancer.Nature genetics · 2026Article
- Article
- Transcriptome-Based Classification of Resected Pancreatic Ductal Adenocarcinoma Enhances Prognostic Modelling Accuracy of Overall Survival Following Adjuvant Treatment.International journal of cancer · 2026Article
- Understanding development and cellular plasticity in the pancreas in health and disease.Nature reviews. Gastroenterology & hepatology · 2026Review
- Microplastics and nanoplastics-related genes signature predicts prognosis in pancreatic ductal adenocarcinoma and functional validation of interleukin 1 alpha.Translational cancer research · 2026Article
- Review
- Dual-oxygen pancreatic cancer organoids recapitulate basal-classical heterogeneity validated by spatial transcriptomics.British journal of cancer · 2026Article
- Evolutionarily Conserved Epigenetic Regulation of Transcriptional Cell States During Vertebrate Pancreatic Tumorigenesis.Cellular and molecular gastroenterology and hepatology · 2026Article
- The Metabolic Rheostat Index Uncovers Pathway-Level Coordination, Immunosuppressive Microenvironment Remodeling, and Therapeutic Co-Vulnerabilities in Pancreatic Ductal Adenocarcinoma.Current issues in molecular biology · 2026Article
315 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
47 authors at 7 institutions in 1 country.
Srivatsan RaghavanDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Harvard Medical School, Boston, MA 02115, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
Peter S WinterDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Institute for Medical Engineering & Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Electronic address: pswinter@mit.edu.
Andrew W NaviaDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Institute for Medical Engineering & Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Hannah L WilliamsDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Harvard Medical School, Boston, MA 02115, USA.
Alan DenAdelCenter for Computational Molecular Biology, Brown University, Providence, RI 02912, USA; Division of Applied Mathematics, Brown University, Providence, RI 02912, USA.
Kristen E LowderDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Jennyfer Galvez-ReyesBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Institute for Medical Engineering & Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Radha L KalekarDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Nolawit MulugetaBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Institute for Medical Engineering & Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Kevin S KapnerDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Manisha S RaghavanDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Ashir A BorahBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Nuo LiuBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Institute for Medical Engineering & Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Sara A VäyrynenDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Harvard Medical School, Boston, MA 02115, USA.
Andressa Dias CostaDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Harvard Medical School, Boston, MA 02115, USA.
Raymond W S NgDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Junning WangDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Emma K HillDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Dorisanne Y RagonDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Lauren K BraisDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Alex M JaegerKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Liam F SpurrDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Yvonne Y LiDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Andrew D CherniackDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Harvard Medical School, Boston, MA 02115, USA.
Matthew A BookerDepartment of Informatics and Analytics, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Elizabeth F CohenDepartment of Informatics and Analytics, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Michael Y TolstorukovDepartment of Informatics and Analytics, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Isaac WakiroDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Asaf RotemDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Center for Cancer Genomics, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Bruce E JohnsonDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Harvard Medical School, Boston, MA 02115, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA; Center for Cancer Genomics, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
James M McFarlandBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Ewa T SicinskaHarvard Medical School, Boston, MA 02115, USA; Department of Oncologic Pathology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Tyler E JacksKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Ryan J SullivanHarvard Medical School, Boston, MA 02115, USA; Massachusetts General Hospital Cancer Center, Boston, MA 02114, USA.
Geoffrey I ShapiroDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Harvard Medical School, Boston, MA 02115, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
Thomas E ClancyDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Harvard Medical School, Boston, MA 02115, USA; Department of Surgery, Brigham and Women's Hospital, Boston, MA 02115, USA.
Kimberly PerezDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Harvard Medical School, Boston, MA 02115, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
Douglas A RubinsonDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Harvard Medical School, Boston, MA 02115, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
Kimmie NgDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Harvard Medical School, Boston, MA 02115, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
James M ClearyDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Harvard Medical School, Boston, MA 02115, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
Lorin CrawfordCenter for Computational Molecular Biology, Brown University, Providence, RI 02912, USA; Department of Biostatistics, Brown University, Providence, RI 02912, USA; Microsoft Research New England, Cambridge, MA 02142, USA.
Scott R ManalisKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
Jonathan A NowakHarvard Medical School, Boston, MA 02115, USA; Center for Cancer Genomics, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA.
Brian M WolpinDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Harvard Medical School, Boston, MA 02115, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
William C HahnDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Harvard Medical School, Boston, MA 02115, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
Andrew J AguirreDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Harvard Medical School, Boston, MA 02115, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA. Electronic address: andrew_aguirre@dfci.harvard.edu.
Alex K ShalekBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Harvard Medical School, Boston, MA 02115, USA; Institute for Medical Engineering & Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA. Electronic address: shalek@mit.edu.
Broad Institute · USBrigham and Women's Hospital · USDana-Farber Cancer Institute · USHarvard University · USMassachusetts Institute of Technology · USBrown University · USMicrosoft (United States) · US
Funding
VIRUS PRODUCTION COREP30CA014051 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI Andreea O'Connell · 1985 to 2026
$93.9MThe Harvard Clinical and Translational Science CenterUL1TR002541 · NCATS · HARVARD MEDICAL SCHOOL · PI NADLER, LEE MARSHALL · 2018 to 2022
$93.0MTissue and Pathology ResourcesP50CA127003 · NCI · DANA-FARBER CANCER INST · PI BASS, ADAM JOEL · 2007 to 2023
$33.2MThe Cellular Geography of Therapeutic Resistance in CancerU2CCA233195 · NCI · DANA-FARBER CANCER INST · PI JOHNSON, BRUCE E. · 2018 to 2023
$13.7MQuantitative and functional characterization of therapeutic resistance in cancerU54CA217377 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI LAUFFENBURGER, DOUGLAS A, MANALIS, SCOTT R · 2017 to 2021
$10.2MCirculating Biomarker Consortium for Pancreatic Cancer Early DetectionU01CA210171 · NCI · DANA-FARBER CANCER INST · PI Michael H. Rosenthal, Brian Matthew Wolpin · 2016 to 2026
$8.7MThe Dana-Farber Cancer Institute Cancer Target Discovery and Development CenterU01CA176058 · NCI · DANA-FARBER CANCER INST · PI HAHN, WILLIAM C. · 2013 to 2021
$7.8MSystematic interrogation of the pancreatic cancer microenvironment in patient-derived specimensU01CA224146 · NCI · DANA-FARBER CANCER INST · PI HAHN, WILLIAM C. · 2017 to 2021
$3.0MDevelopment and implementation of multiplex methods to understand the biology and heterogeneity of patient-derived cancer modelsU01CA250549 · NCI · DANA-FARBER CANCER INST · PI HAHN, WILLIAM C. · 2020 to 2022
$2.9MFunctional interrogation of epigenetic vulnerabilities in KRAS-mutant pancreatic cancerK08CA218420 · NCI · DANA-FARBER CANCER INST · PI AGUIRRE, ANDREW JAMES · 2017 to 2021
$886kExploring the impact of HSP90 inhibition on antigen presentation and anti-tumor immune responsesR00CA241072 · NCI · H. LEE MOFFITT CANCER CTR & RES INST · PI JAEGER, ALEX · 2022 to 2024
$742kExploring the impact of HSP90 inhibition on antigen presentation and anti-tumor immune responsesK99CA241072 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI JAEGER, ALEX · 2020 to 2021
$300kNCATS NIH HHS UL1 TR002541NCI NIH HHS K08 CA218420NCI NIH HHS K99 CA241072NCI NIH HHS P30 CA014051NCI NIH HHS P50 CA127003NCI NIH HHS R00 CA241072NCI NIH HHS U01 CA176058NCI NIH HHS U01 CA210171NCI NIH HHS U01 CA224146NCI NIH HHS U01 CA250549NCI NIH HHS U2C CA233195NCI NIH HHS U54 CA217377
Abstract
Prognostically relevant RNA expression states exist in pancreatic ductal adenocarcinoma (PDAC), but our understanding of their drivers, stability, and relationship to therapeutic response is limited. To examine these attributes systematically, we profiled metastatic biopsies and matched organoid models at single-cell resolution. In vivo, we identify a new intermediate PDAC transcriptional cell state and uncover distinct site- and state-specific tumor microenvironments (TMEs). Benchmarking models against this reference map, we reveal strong culture-specific biases in cancer cell transcriptional state representation driven by altered TME signals. We restore expression state heterogeneity by adding back in vivo-relevant factors and show plasticity in culture models. Further, we prove that non-genetic modulation of cell state can strongly influence drug responses, uncovering state-specific vulnerabilities. This work provides a broadly applicable framework for aligning cell states across in vivo and ex vivo settings, identifying drivers of transcriptional plasticity and manipulating cell state to target associated vulnerabilities.
Indexed as
Tumor MicroenvironmentAdultAgedBiomarkers, TumorCarcinoma, Pancreatic DuctalCell Line, TumorFemaleGene Expression Regulation, NeoplasticHumansMaleMiddle AgedPancreatic NeoplasmsSingle-Cell AnalysisBiomarkers, Tumorliver metastasespancreatic cancerpatient-derived organoid modelsplasticitysingle-cell RNA-sequencingtranscriptional statestumor heterogeneitytumor microenvironment
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