{
  "abstract": "Transcriptional states can provide functional information beyond genomic alterations, but whether states derived from nonmalignant physiological perturbations remain informative in cancer is unclear. We separated global RNA-output suppression from relative transcriptional remodeling induced by dihydrotestosterone in mouse adrenal zona fasciculata cells and derived a cross-sex transcriptional signature. Projection of this signature to human orthologs defined an androgen-suppressed transcriptional state (ASTS) across cancer cell lines. Integration with pharmacogenomic and CRISPR dependency datasets showed that higher ASTS was associated with resistance to EGFR-targeted drugs and reduced EGFR dependency, together with increased dependency on mitochondrial pathways, including mitochondrial translation and respiratory electron transport. These associations were not attributable to a single major cancer lineage and remained evident after adjustment for canonical oncogenic drivers and cell-state covariates. ASTS provides a proof of concept that an endocrine-derived transcriptional state can reveal candidate functional vulnerabilities in an unrelated cancer context.",
  "abstract_shown": true,
  "affiliations": [
    "Graduate School of Medical Sciences, Kyushu University"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 2,
  "authors": [
    {
      "name": "Y. Miao"
    },
    {
      "affs": [
        0
      ],
      "name": "T. Baba"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/egtda2g6dxrw9.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.06.757186",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.06.757186v1.full",
  "id": "egtda2g6dxrw9",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.06.757186v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "cancer biology"
    ],
    [
      "openalex",
      "2740|Prostate Cancer Treatment and Research"
    ]
  ],
  "openalex": "W7220848180",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.06.757186v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-06",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/egtda2g6dxrw9.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:26:25Z",
      "native_id": "10.64898/2026.10.06.757186",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.06.757186v2"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "biorxiv:cancer biology",
      "subfield": "oncology"
    }
  ],
  "title": "An androgen-derived transcriptional state reveals signaling and mitochondrial vulnerabilities in cancer",
  "title_text": "An androgen-derived transcriptional state reveals signaling and mitochondrial vulnerabilities in cancer",
  "type": "preprint",
  "updated_at": "2026-10-30T12:27:41Z",
  "url": "https://research.draconitic.com/paper/egtda2g6dxrw9",
  "venue": "bioRxiv",
  "versions": []
}