{
  "abstract": "Genomic stratification leaves most patients with colorectal cancer (CRC) without opportunities for targeted therapy. Seeking tumour state-linked drug sensitivities, we combined image-based ex vivo drug profiling with matched transcriptomics in 127 prospectively collected patient biopsies across CRC stages and molecular subtypes. Network-level integration identified a ciliogenic cell state defined by upregulation of cilia related genes with selective sensitivity to the FGFR inhibitor erdafitinib. This ciliogenic signature was associated with poor progression-free survival (hazard ratio 2.28; adjusted p=0.0098), even in early-stage colorectal cancer. Furthermore, knockdown of the transcriptional regulators RFX2 and RFX3, upstream of the ciliogenic cell state, attenuated erdafitinib sensitivity. Orthogonal bulk and single-cell analyses across normal, primary and metastatic tissues contextualised the ciliogenic programme along a transition from canonical epithelial states towards fetal and non-canonical tumour states, concomitant with Wnt-related remodelling, FGFR1/FGFR2 upregulation, and loss of intestinal epithelial identity. Together, these findings define a tumour-intrinsic ciliogenic cell state as a feature of CRC progression, revealing a patient-stratified repurposing opportunity for targeted therapy beyond the current CRC treatment paradigms.",
  "abstract_shown": true,
  "affiliations": [
    "Botnar Institute of Immune Engineering"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 16,
  "authors": [
    {
      "name": "L. Kralickova"
    },
    {
      "name": "N. Miglino"
    },
    {
      "name": "C. Esposito"
    },
    {
      "name": "R. Pfaendler"
    },
    {
      "name": "R. Wegmann"
    },
    {
      "name": "P. Ballesteros Cuartero"
    },
    {
      "name": "J. Mena"
    },
    {
      "name": "F. Panebianco"
    },
    {
      "name": "L. A. Boos"
    },
    {
      "name": "U. Richter"
    },
    {
      "name": "P. Rahimzadeh"
    },
    {
      "name": "T. Mehra"
    },
    {
      "name": "V. H. Koelzer"
    },
    {
      "name": "S. Piscuoglio"
    },
    {
      "name": "A. Wicki"
    },
    {
      "affs": [
        0
      ],
      "name": "B. Snijder"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/d6xqbkznv1v48.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.12.756637",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.12.756637v1.full",
  "id": "d6xqbkznv1v48",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.12.756637v1",
  "language": null,
  "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"
    ],
    [
      "openalex",
      "2730|Colorectal Cancer Treatments and Studies"
    ]
  ],
  "openalex": "W7221646633",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.12.756637v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-12",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/d6xqbkznv1v48.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:27:37Z",
      "native_id": "10.64898/2026.10.12.756637",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.12.756637v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "biorxiv:cancer biology",
      "subfield": "oncology"
    }
  ],
  "title": "An RFX-driven ciliogenic cell state defines ex vivo FGFR-inhibitor sensitivity in colorectal cancer",
  "title_text": "An RFX-driven ciliogenic cell state defines ex vivo FGFR-inhibitor sensitivity in colorectal cancer",
  "type": "preprint",
  "updated_at": "2026-10-30T12:27:37Z",
  "url": "https://research.draconitic.com/paper/d6xqbkznv1v48",
  "venue": "bioRxiv",
  "versions": []
}