ArticleNature biomedical engineering2025
Heterogeneity-driven phenotypic plasticity and treatment response in branched-organoid models of pancreatic ductal adenocarcinoma.
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Article in Nature biomedical engineering, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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37 citing papers in PubMed.
- Tutorial: interrogating biology using organoid technologies.Nature protocols · 2026Review
- Overcoming cancer resistance in pancreatic cancer: toward dynamic precision oncology.Molecular biology reports · 2026Review
- Emerging organoids and organoids-on-chip platforms for translational development of antibody‒drug conjugates and next-generation bioconjugates.Acta pharmaceutica Sinica. B · 2026Review
- Pulmonary Metastases After Surgical Resection of Pancreatic Ductal Adenocarcinoma: Impact on Long-Term Survival and Perspectives on Targeted Treatments.Annals of surgical oncology · 2026Article
- Bioengineering advances in pancreatic cancer organoids for reproducible tumor microenvironment modeling.iScience · 2026Review
- Radioluminescence microscopy of tumor organoids enabled by a reconfigurable high-resolution imaging setup.EJNMMI research · 2026Article
- Pancreatic organoids and organoid-on-a-chip platforms: from disease modeling to precision therapy.Journal of translational medicine · 2026Review
- Tumor organoids as a revolutionary platform for advancing cancer nanomedicine.Molecular cancer · 2026Review
- Arp2/3 complex and β1 integrin drive an invasive front through extracellular matrix adaptation in pancreatic cancer.International journal of cancer · 2026Article
- Pancreatic cancer.Nature reviews. Disease primers · 2026Review
- Bottom-Up Programming of Cell States in Cancer Organoids with Defined Synthetic Adhesion Cues.Advanced materials (Deerfield Beach, Fla.) · 2026Article
- Impact of culture dimensionality and matrix composition on morphology, phenotype and drug response in pancreatic cancer models.Scientific reports · 2026Article
- GRIP-Lung: Generative Model of Response to Drug-Induced Perturbation in Lung Cancer.International journal of molecular sciences · 2026Article
- A novel biomacromolecule-predominated hybrid unit: from design, characterization to application.National science review · 2026Article
- Proceedings of the ... AAAI Conference on Artificial Intelligence. AAAI Conference on Artificial Intelligence · 2026Article
- A Patient-Derived Organ-on-Chip Platform for Modeling the Tumor Microenvironment and Drug Responses in Pancreatic Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Metabolomic profiling and anti-tumor function of canine NK cells in tumor interaction.BMC veterinary research · 2026Article
- Epigenetic and transcriptional control of classical and basal-like cell states in pancreatic ductal adenocarcinoma.Gastroenterology report · 2026Review
- Organoids glimpse: the nexus for diverse tumor heterogeneity.Frontiers in cell and developmental biology · 2026Review
- Advances in liver and pancreas organoids: how far we have come and where we go next.Nature reviews. Gastroenterology & hepatology · 2026Review
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Authors and funding
44 authors.
Aristeidis PapargyriouTranslational Pancreatic Cancer Research Center, Klinik und Poliklinik für Innere Medizin II, Klinikum rechts der Isar, Technical University of Munich, München, Germany.ORCID http://orcid.org/0000-0002-2577-4737
Mulham NajajrehTranslational Pancreatic Cancer Research Center, Klinik und Poliklinik für Innere Medizin II, Klinikum rechts der Isar, Technical University of Munich, München, Germany.
David P CookDepartment of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
Carlo H MaurerTranslational Pancreatic Cancer Research Center, Klinik und Poliklinik für Innere Medizin II, Klinikum rechts der Isar, Technical University of Munich, München, Germany.
Stefanie BärthelCenter for Translational Cancer Research (TranslaTUM), School of Medicine, Technical University of Munich, Munich, Germany.ORCID http://orcid.org/0000-0001-5986-4864
Hendrik A MessalDivision of Molecular Pathology, Oncode Institute, The Netherlands Cancer Institute, Amsterdam, the Netherlands.ORCID http://orcid.org/0000-0003-2259-0286
Sakthi K RavichandranTranslational Pancreatic Cancer Research Center, Klinik und Poliklinik für Innere Medizin II, Klinikum rechts der Isar, Technical University of Munich, München, Germany.
Till RichterInstitute of Computational Biology, Helmholtz Center Munich, Neuherberg, Germany.ORCID http://orcid.org/0000-0001-6008-8209
Moritz KnolleInstitute of Diagnostic and Interventional Radiology, Klinikum rechts der Isar München, Technical University of Munich, Munich, Germany.
Thomas MetzlerComparative Experimental Pathology, Institut für Allgemeine Pathologie und Pathologische Anatomie, School of Medicine, Technical University of Munich, Munich, Germany.ORCID http://orcid.org/0000-0002-1620-5559
Akul R ShastriTranslational Pancreatic Cancer Research Center, Klinik und Poliklinik für Innere Medizin II, Klinikum rechts der Isar, Technical University of Munich, München, Germany.
Rupert ÖllingerCenter for Translational Cancer Research (TranslaTUM), School of Medicine, Technical University of Munich, Munich, Germany.
Jacob JasperTranslational Pancreatic Cancer Research Center, Klinik und Poliklinik für Innere Medizin II, Klinikum rechts der Isar, Technical University of Munich, München, Germany.
Laura SchmidleitnerTranslational Pancreatic Cancer Research Center, Klinik und Poliklinik für Innere Medizin II, Klinikum rechts der Isar, Technical University of Munich, München, Germany.
Surui WangInstitute for Diabetes and Cancer, Helmholtz Center Munich, Neuherberg, Germany.
Christian SchneeweisCenter for Translational Cancer Research (TranslaTUM), School of Medicine, Technical University of Munich, Munich, Germany.
Hellen Ishikawa-AnkerholdDepartment of Medicine I, University Hospital of the Ludwig-Maximilians-University Munich, Munich, Germany.
Thomas EngleitnerCenter for Translational Cancer Research (TranslaTUM), School of Medicine, Technical University of Munich, Munich, Germany.
Laura MataiteTranslational Pancreatic Cancer Research Center, Klinik und Poliklinik für Innere Medizin II, Klinikum rechts der Isar, Technical University of Munich, München, Germany.
Mariia SeminaInstitute of Diagnostic and Interventional Radiology, Klinikum rechts der Isar München, Technical University of Munich, Munich, Germany.
Hussein TrabulssiInstitute of Diagnostic and Interventional Radiology, Klinikum rechts der Isar München, Technical University of Munich, Munich, Germany.
Sebastian LangeKlinik und Poliklinik für Innere Medizin II, Klinikum rechts der Isar, Technical University of Munich, München, Germany.ORCID http://orcid.org/0000-0003-0406-1401
Aashreya RavichandraTranslational Pancreatic Cancer Research Center, Klinik und Poliklinik für Innere Medizin II, Klinikum rechts der Isar, Technical University of Munich, München, Germany.
Maximilian SchusterTranslational Pancreatic Cancer Research Center, Klinik und Poliklinik für Innere Medizin II, Klinikum rechts der Isar, Technical University of Munich, München, Germany.ORCID http://orcid.org/0000-0001-9030-2210
Sebastian MuellerCenter for Translational Cancer Research (TranslaTUM), School of Medicine, Technical University of Munich, Munich, Germany.ORCID http://orcid.org/0009-0008-1514-3027
Katja PeschkeTranslational Pancreatic Cancer Research Center, Klinik und Poliklinik für Innere Medizin II, Klinikum rechts der Isar, Technical University of Munich, München, Germany.
Arlett SchäferTranslational Pancreatic Cancer Research Center, Klinik und Poliklinik für Innere Medizin II, Klinikum rechts der Isar, Technical University of Munich, München, Germany.ORCID http://orcid.org/0000-0002-8010-594X
Sophie DobiaschDepartment of Radiation Oncology, Technical University of Munich, Munich, Germany.
Stephanie E CombsDepartment of Radiation Oncology, Technical University of Munich, Munich, Germany.
Roland M SchmidKlinik und Poliklinik für Innere Medizin II, Klinikum rechts der Isar, Technical University of Munich, München, Germany.
Andreas R BauschCenter for Functional Protein Assemblies, Technical University of Munich, Garching, Germany.ORCID http://orcid.org/0000-0002-4608-9544
Rickmer BrarenInstitute of Diagnostic and Interventional Radiology, Klinikum rechts der Isar München, Technical University of Munich, Munich, Germany.
Irina HeidInstitute of Diagnostic and Interventional Radiology, Klinikum rechts der Isar München, Technical University of Munich, Munich, Germany.
Christina H ScheelInstitute of Stem Cell Research, Helmholtz Center Munich, Neuherberg, Germany.
Günter SchneiderDepartment of General, Visceral and Pediatric Surgery, University Medical Center Göttingen, Göttingen, Germany.ORCID http://orcid.org/0000-0003-1840-4508
Anja ZeigererInstitute for Diabetes and Cancer, Helmholtz Center Munich, Neuherberg, Germany.
Malte D LueckenInstitute of Computational Biology, Helmholtz Center Munich, Neuherberg, Germany.
Katja SteigerComparative Experimental Pathology, Institut für Allgemeine Pathologie und Pathologische Anatomie, School of Medicine, Technical University of Munich, Munich, Germany.ORCID http://orcid.org/0000-0002-7269-5433
Georgios KaissisInstitute of Diagnostic and Interventional Radiology, Klinikum rechts der Isar München, Technical University of Munich, Munich, Germany.ORCID http://orcid.org/0000-0001-8382-8062
Jacco van RheenenDivision of Molecular Pathology, Oncode Institute, The Netherlands Cancer Institute, Amsterdam, the Netherlands.ORCID http://orcid.org/0000-0001-8175-1647
Fabian J TheisInstitute of Computational Biology, Helmholtz Center Munich, Neuherberg, Germany.ORCID http://orcid.org/0000-0002-2419-1943
Dieter SaurCenter for Translational Cancer Research (TranslaTUM), School of Medicine, Technical University of Munich, Munich, Germany.ORCID http://orcid.org/0000-0001-5874-0210
Roland RadCenter for Translational Cancer Research (TranslaTUM), School of Medicine, Technical University of Munich, Munich, Germany.ORCID http://orcid.org/0000-0002-6849-9659
Maximilian ReichertTranslational Pancreatic Cancer Research Center, Klinik und Poliklinik für Innere Medizin II, Klinikum rechts der Isar, Technical University of Munich, München, Germany. maximilian.reichert@tum.de.ORCID http://orcid.org/0000-0002-8611-5639
Funding
No grant is acknowledged in the PubMed record.
Abstract
In patients with pancreatic ductal adenocarcinoma (PDAC), intratumoural and intertumoural heterogeneity increases chemoresistance and mortality rates. However, such morphological and phenotypic diversities are not typically captured by organoid models of PDAC. Here we show that branched organoids embedded in collagen gels can recapitulate the phenotypic landscape seen in murine and human PDAC, that the pronounced molecular and morphological intratumoural and intertumoural heterogeneity of organoids is governed by defined transcriptional programmes (notably, epithelial-to-mesenchymal plasticity), and that different organoid phenotypes represent distinct tumour-cell states with unique biological features in vivo. We also show that phenotype-specific therapeutic vulnerabilities and modes of treatment-induced phenotype reprogramming can be captured in phenotypic heterogeneity maps. Our methodology and analyses of tumour-cell heterogeneity in PDAC may guide the development of phenotype-targeted treatment strategies.
Indexed as
Carcinoma, Pancreatic DuctalOrganoidsPancreatic NeoplasmsAnimalsCell Line, TumorEpithelial-Mesenchymal TransitionHumansMicePhenotype
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