{
  "abstract": "Pancreatic ductal adenocarcinoma (PDAC) develops chemoresistance through dynamic cell-state transitions, yet the regulatory network architecture governing drug-tolerant states remains poorly characterised, because static expression snapshots cannot capture how interaction topology evolves along treatment-induced trajectories. We established a 3D PANC-1 tissue model on decellularised porcine intestinal matrix, which reaches patient-like proliferation indices and tissue-niche-specific drug responses, and performed single-cell RNA sequencing across four conditions: control, gemcitabine (GEM), TGF-β1, and their combination. Coupling pseudotime trajectory inference to dynamic protein-protein interaction network analysis, we tracked betweenness centrality continuously across cell-state transitions rather than comparing discrete states. GEM survivors engaged a proliferative programme (E2F1, CDK1, AURKA, TPX2, TOP2A, BIRC5), whereas TGF-β1 induced an independent EMT attractor (SPOCK1, MBOAT2, COL5A1, THBS1, FN1). Where the two converged, an emergent bottleneck appeared: CDK1 betweenness centrality spiked selectively, restrained by CDKN1A (p21) and WEE1, defining an S-phase-persistence state enriched for GEM survivors. Cross-examination in a PDAC atlas of 726,107 cells from 231 patients showed 8.7-fold metastatic enrichment of triple-positive cells. This framework, linking controlled 3D tissue experimentation, single-cell systems analysis and clinical-scale patient data, is applicable to drug resistance across cancer types.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Bioinformatics, Biocenter, University of Würzburg, Am Hubland, Würzburg, Germany.",
    "Department for Functional Materials in Medicine and Dentistry, University Hospital Würzburg, Würzburg, Germany.",
    "Section for Molecular Medicine of Signal Transduction, Institute of Molecular Medicine, Faculty of Medicine, Martin Luther University Halle-Wittenberg, 06120, Halle (Saale), Germany.",
    "Department of Bioinformatics, Biocenter, University of Würzburg, Am Hubland, Würzburg, Germany. johannes.balkenhol@uni-wuerzburg.de."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Maryam Almasi"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Jesús Guillermo Nieves Pereira",
      "orcid": "0000-0002-1267-7049"
    },
    {
      "affs": [
        0
      ],
      "name": "Thomas Dandekar"
    },
    {
      "affs": [
        1
      ],
      "name": "Gudrun Dandekar",
      "orcid": "0000-0001-6127-5794"
    },
    {
      "affs": [
        3
      ],
      "name": "Johannes Balkenhol"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/6kyfaeb8yk7h4.bib",
  "cited_by": 0,
  "doi": "10.1038/s41540-026-00830-z",
  "fulltext_url": "https://europepmc.org/articles/PMC13694714",
  "id": "6kyfaeb8yk7h4",
  "issns": [
    "2056-7189"
  ],
  "landing_url": "https://europepmc.org/article/MED/42919864",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "lcc",
      "QH301-705.5"
    ],
    [
      "openalex",
      "2730|Pancreatic and Hepatic Oncology Research"
    ]
  ],
  "openalex": "W7223281718",
  "pdf_url": "https://europepmc.org/articles/PMC13694714?pdf=render",
  "pmcid": "PMC13694714",
  "pmid": "42919864",
  "published": "2026-10-23",
  "publisher": "Nature Portfolio",
  "ris": "https://research.draconitic.com/paper/6kyfaeb8yk7h4.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:33Z",
      "native_id": "MED:42919864",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42919864"
    },
    {
      "first_seen": "2026-10-30T13:46:01Z",
      "native_id": "3128f0addec2482994179a82052a6658",
      "source": "doaj",
      "url": "https://doi.org/10.1038/s41540-026-00830-z"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|Pancreatic and Hepatic Oncology Research",
      "subfield": "oncology"
    }
  ],
  "title": "3D tissue model to patient atlas: dynamic network topology reveals PDAC chemoresistance bottlenecks.",
  "title_text": "3D tissue model to patient atlas: dynamic network topology reveals PDAC chemoresistance bottlenecks.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T13:46:01Z",
  "url": "https://research.draconitic.com/paper/6kyfaeb8yk7h4",
  "venue": "NPJ systems biology and applications",
  "versions": []
}