{
  "abstract": "Tumors are highly complex dynamic ecosystems with causal relationships between cancer cells and their tumor microenvironment (TME). To disentangle these interactions, we performed long-term co-culture experiments with cancer cells evolving alongside continuously replenished fibroblasts or macrophages. This allowed us to distinguish between adaptive and physiological responses in specific cancer-TME interactions, which we then also recapitulated in patient tumors. We found that co-culture with fibroblasts induced the epithelial-mesenchymal transition in cancer cells and resulted in their increased drug tolerance, while co-culture with macrophages promoted stress, hypoxia responses and enhanced tumorigenicity. Adaptations were recurrent and partially reversible, but could not be explained by clonal selection, suggesting a dynamic non-mutational process. Moreover, adapted cancer cells elicited cell state changes in the fibroblasts and macrophages consistent with an extended phenotype mode of cancer evolution. Our findings reframe cancer-TME interactions by a systematic dissection according to sets of specific adaptations and programmed responses.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 14,
  "authors": [
    {
      "name": "Maayan Pour",
      "orcid": "0000-0003-1997-5193"
    },
    {
      "name": "Guisheng Zhao"
    },
    {
      "name": "Angeliki Karatza",
      "orcid": "0009-0004-9271-4576"
    },
    {
      "name": "Gustavo S. França",
      "orcid": "0000-0001-5262-1309"
    },
    {
      "name": "Jingye Wang"
    },
    {
      "name": "Linda Procell",
      "orcid": "0009-0000-8025-0218"
    },
    {
      "name": "Anjali Rao"
    },
    {
      "name": "Deborah A. Corcoran",
      "orcid": "0000-0002-5029-0611"
    },
    {
      "name": "Ayushi S. Patel",
      "orcid": "0000-0002-4959-5397"
    },
    {
      "name": "Cristina H. Hajdu",
      "orcid": "0000-0002-2856-9966"
    },
    {
      "name": "Kwok-Kin Wong",
      "orcid": "0000-0001-6323-235X"
    },
    {
      "name": "Amanda W. Lund",
      "orcid": "0000-0001-7389-9983"
    },
    {
      "name": "Edna Cukierman",
      "orcid": "0000-0002-1452-9576"
    },
    {
      "name": "Itai Yanai",
      "orcid": "0000-0002-8438-2741"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/az63c34pf35xn.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.27.762245",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.27.762245v1.full",
  "id": "az63c34pf35xn",
  "issns": [
    "2692-8205"
  ],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.27.762245v1",
  "language": "en",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "cancer biology"
    ],
    [
      "heading",
      "Article"
    ]
  ],
  "openalex": null,
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.27.762245v1.full.pdf",
  "pmcid": "PMC13733992",
  "pmid": "42990428",
  "published": "2026-10-27",
  "publisher": "Cold Spring Harbor Laboratory Preprints",
  "ris": "https://research.draconitic.com/paper/az63c34pf35xn.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:30:30Z",
      "native_id": "10.64898/2026.10.27.762245",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.27.762245v1"
    },
    {
      "first_seen": "2026-11-08T12:23:39Z",
      "native_id": "PMC13733992",
      "source": "pmc",
      "url": "https://doi.org/10.64898/2026.10.27.762245"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "biorxiv:cancer biology",
      "subfield": "oncology"
    }
  ],
  "title": "Cancer cell adaptations along a proliferation-robustness axis drive TME pro-tumor phenotypes",
  "title_text": "Cancer cell adaptations along a proliferation-robustness axis drive TME pro-tumor phenotypes",
  "type": "preprint",
  "updated_at": "2026-11-08T12:23:39Z",
  "url": "https://research.draconitic.com/paper/az63c34pf35xn",
  "venue": "bioRxiv",
  "versions": []
}