{
  "abstract": "There are no adequate carcinogen-induced models of the earliest stages of human squamous lung cancer (LUSC), limiting the development of effective chemoprevention strategies. We developed a novel human model of early LUSC by exposing differentiated primary human airway cells to a chemical carcinogen known to cause murine LUSC. Carcinogen exposure induced a phenotype recapitulating the earliest stages of human LUSC and associated with the emergence of a novel population of atypical basal cells (ABCs). ABCs express key cancer hallmark markers but without evidence of either common LUSC-associated mutations or an emergent major clonal/subclonal population. We established the clinical relevance of this model by demonstrating enrichment of the ABC expression profile in independent clinical precancer specimens. We then show that capivasertib, a clinically approved kinase inhibitor, prevented the emergence of the abnormal phenotype and the accumulation of cells with an active DNA damage response. Further, capivasertib reversed the established phenotype; and remained effective when nebulised in vitro, mimicking therapeutic inhalation. Together, these findings establish a tractable human model of carcinogen-induced early LUSC and provide a proof-of-principle for repurposing targeted therapies for the prevention of lung cancer.",
  "abstract_shown": true,
  "affiliations": [
    "University of Cambridge"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 16,
  "authors": [
    {
      "name": "W. Guo"
    },
    {
      "name": "H. Giles"
    },
    {
      "name": "A. Chernaik"
    },
    {
      "name": "Y. Memari"
    },
    {
      "name": "J. Xie"
    },
    {
      "name": "D. Black"
    },
    {
      "name": "A. Hilgendorff"
    },
    {
      "name": "C. Gabriel"
    },
    {
      "name": "A. O. Yildirim"
    },
    {
      "name": "H. Davies"
    },
    {
      "name": "M. Goddard"
    },
    {
      "name": "L. D'Sa"
    },
    {
      "name": "O. Schmid"
    },
    {
      "name": "S. Nik-Zainal"
    },
    {
      "name": "N. Han"
    },
    {
      "affs": [
        0
      ],
      "name": "F. McCaughan"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/2jqwy2d917mz7.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.17.748423",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.17.748423v1.full",
  "id": "2jqwy2d917mz7",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.17.748423v1",
  "language": null,
  "licence": "CC-BY-NC",
  "licence_label": "CC BY-NC",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "cancer biology"
    ],
    [
      "openalex",
      "2730|Lung Cancer Research Studies"
    ]
  ],
  "openalex": "W7213538184",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.17.748423v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-17",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/2jqwy2d917mz7.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:23:04Z",
      "native_id": "10.64898/2026.09.17.748423",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.17.748423v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "biorxiv:cancer biology",
      "subfield": "oncology"
    }
  ],
  "title": "Carcinogen-induced preinvasive human squamous lung cancer is characterised by a novel atypical basal cell state and presents opportunities for chemoprevention",
  "title_text": "Carcinogen-induced preinvasive human squamous lung cancer is characterised by a novel atypical basal cell state and presents opportunities for chemoprevention",
  "type": "preprint",
  "updated_at": "2026-10-30T12:23:04Z",
  "url": "https://research.draconitic.com/paper/2jqwy2d917mz7",
  "venue": "bioRxiv",
  "versions": []
}