{
  "abstract": "Overcoming resistance to standard‐of‐care chemotherapy represents an unmet need in oncology. To help address this challenge, here we established and characterized a panel of human cisplatin‐resistant lung and breast cancer cell lines and patient‐derived organoids from high‐grade serous ovarian carcinomas (HGSOC), and show that platinum resistance can be overcome by treatment with diethyldithiocarbamate‐copper (CuET), a metabolite of the alcohol‐aversion drug disulfiram. All platinum‐resistant models remained sensitive to CuET, consistent with distinct cytotoxicity mechanisms: proteotoxic stress for CuET and DNA damage for cisplatin, respectively. Platinum adduct and DNA damage response analyses suggested diverse mechanisms of cisplatin resistance among our models. Considering potential CuET‐based therapies, our gene knock‐down and functional assays in preclinical models, complemented with immunohistochemical analysis of tissue samples from cohorts of triple‐negative breast cancer and HGSOC patients indicate that levels of metallothioneins, rather than NPL4 (the molecular target of CuET) warrant further evaluation as candidate biomarkers of CuET sensitivity. This dataset provides a resource of platinum‐resistant models of common carcinomas, identifies CuET as a compound overcoming such resistance and provides leads for predictive biomarker discovery, with potential clinical implications in oncology.",
  "abstract_shown": true,
  "affiliations": [
    "Genome Integrity Group Danish Cancer Institute, Danish Cancer Society Copenhagen Denmark",
    "Division of Genome Biology, Department of Medical Biochemistry and Biophysics, Science for Life Laboratory Karolinska Institute Stockholm Sweden",
    "Cancer Invasion and Resistance Group Danish Cancer Institute, Danish Cancer Society Copenhagen Denmark",
    "Faculty of Medicine and Dentistry Institute of Molecular and Translational Medicine, Palacky University Olomouc Czech Republic",
    "Department of Pathology Complejo Hospitalario Universitario Insular Las Palmas Gran Canaria Spain",
    "Molecular Unit, Department of Pathology Copenhagen University Hospital, Herlev and Gentofte Hospital Denmark",
    "Department of Gynaecology Copenhagen University Hospital Rigshospitalet Denmark",
    "Department of Clinical Medicine University of Copenhagen Denmark",
    "Department of Pathology Copenhagen University Hospital Rigshospitalet Denmark",
    "Virus, Lifestyle and Genes Group Danish Cancer Institute, Danish Cancer Society Copenhagen Denmark",
    "Translational and Clinical Pharmacology, Department of Drug Design and Pharmacology University of Copenhagen Denmark",
    "Division of Cancer Research, Ninewells Hospital and Medical School University of Dundee UK"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 21,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Stefanos Arampatzis",
      "orcid": "0009-0004-2393-4575"
    },
    {
      "affs": [
        0
      ],
      "name": "Tereza Buchtová",
      "orcid": "0000-0001-5233-1504"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Jirina Bartkova"
    },
    {
      "affs": [
        2
      ],
      "name": "Marie Lund Bay"
    },
    {
      "affs": [
        0
      ],
      "name": "Christoffer Lynge Halvorsen",
      "orcid": "0009-0003-3223-0775"
    },
    {
      "affs": [
        0
      ],
      "name": "Zuzana Machacova"
    },
    {
      "affs": [
        3
      ],
      "name": "Zdenek Skrott"
    },
    {
      "affs": [
        3
      ],
      "name": "Martin Mistrik",
      "orcid": "0000-0002-2321-0348"
    },
    {
      "affs": [
        0
      ],
      "name": "Ekaterina Dulina"
    },
    {
      "affs": [
        4
      ],
      "name": "Miguel Andujar‐Sanchez"
    },
    {
      "affs": [
        5
      ],
      "name": "Estrid Høgdall"
    },
    {
      "affs": [
        6
      ],
      "name": "Tine Henrichsen Schnack"
    },
    {
      "affs": [
        6,
        7
      ],
      "name": "Claus Høgdall"
    },
    {
      "affs": [
        6
      ],
      "name": "Berit Jul Mosgaard"
    },
    {
      "affs": [
        8
      ],
      "name": "Marie Boennelycke"
    },
    {
      "affs": [
        6
      ],
      "name": "Jacob Brink Laursen"
    },
    {
      "affs": [
        9
      ],
      "name": "Allan Jensen"
    },
    {
      "affs": [
        6,
        7,
        9
      ],
      "name": "Susanne K. Kjær"
    },
    {
      "affs": [
        2,
        10
      ],
      "name": "Tuula Kallunki"
    },
    {
      "affs": [
        0
      ],
      "name": "Robert Strauss",
      "orcid": "0000-0003-1777-7177"
    },
    {
      "affs": [
        0,
        1,
        11
      ],
      "name": "Jiri Bartek",
      "orcid": "0000-0003-2013-7525"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/1x9bw63223xq0.bib",
  "cited_by": 0,
  "doi": "10.1002/1878-0261.70356",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13732508/",
  "id": "1x9bw63223xq0",
  "issns": [
    "1574-7891",
    "1878-0261"
  ],
  "landing_url": "https://doi.org/10.1002/1878-0261.70356",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Cancer Therapy Resistance"
    ],
    [
      "heading",
      "Research Article"
    ],
    [
      "openalex",
      "2730|Metal complexes synthesis and properties"
    ]
  ],
  "openalex": "W7225226616",
  "pdf_url": null,
  "pmcid": "PMC13732508",
  "pmid": "42979729",
  "published": "2026-11-04",
  "publisher": "Wiley",
  "ris": "https://research.draconitic.com/paper/1x9bw63223xq0.ris",
  "sources": [
    {
      "first_seen": "2026-11-08T12:22:29Z",
      "native_id": "PMC13732508",
      "source": "pmc",
      "url": "https://doi.org/10.1002/1878-0261.70356"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|Metal complexes synthesis and properties",
      "subfield": "oncology"
    }
  ],
  "title": "Overcoming platinum resistance by the disulfiram metabolite CuET in novel preclinical models of human carcinomas",
  "title_text": "Overcoming platinum resistance by the disulfiram metabolite CuET in novel preclinical models of human carcinomas",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T12:22:29Z",
  "url": "https://research.draconitic.com/paper/1x9bw63223xq0",
  "venue": "Molecular Oncology",
  "versions": []
}