{
  "abstract": "Despite advances in precision oncology, effective personalized treatments are still lacking for most patients with cancer1. The Cancer Dependency Map (DepMap) accelerates this field by systematically identifying cancer vulnerabilities in diverse preclinical models. Data from over 1,300 cell lines have led to the discovery of new therapeutic strategies across multiple tumour types2. However, mapping cancer vulnerabilities using traditional cell lines has limitations, including insufficient cancer subtype representation and the impact of culture conditions on perturbation responses. Here we perform 147 genome-scale CRISPR screens and multi-omic characterizations of next-generation (NextGen) cancer models (organoids and spheroids) across 10 cancer types. This strategy enables the expansion of DepMap to cover new genomic and molecular subtypes and to identify new biomarker-associated vulnerabilities. These new models also preserve transcriptional programs that are silenced in traditional cell lines and facilitate the discovery of specific gene dependencies associated with these programs. Comparisons of traditional and NextGen cancer models enable further identification of distinct effects of growth format and culture medium on gene essentiality. The integrated dataset combines data from both model types to offer a valuable, expansive resource for exploring cancer vulnerabilities and is accessible via the DepMap portal. Integration of genome-scale CRISPR screening data from traditional cell lines and next-generation cancer models expands the representation of tumour subtypes and genomic alterations in The Cancer Dependency Map.",
  "abstract_shown": true,
  "affiliations": [
    "Broad Institute of MIT and Harvard, Cambridge, MA, USA",
    "Department of Pathology, Dana-Farber Cancer Institute, Boston, MA, USA",
    "Group of Biomedical Research in Gynecology, Vall d'Hebron Institute of Research (VHIR), Instituto de Investigación Sanitaria Hospital Universitari Vall d'Hebron (IIS IR-HUVH), Universitat Autònoma de Barcelona, CIBERONC, Barcelona, Spain",
    "Department of Bioengineering, Northeastern University, Boston, MA, USA",
    "Department of Mechanical and Industrial Engineering, Northeastern University, Boston, MA, USA",
    "Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia",
    "Personalised Oncology Division, Walter and Eliza Hall Institute, Parkville, Victoria, Australia",
    "Department of Systems Biology, Harvard Medical School, Boston, MA, USA",
    "Laboratory of Systems Pharmacology, Harvard Program in Therapeutic Science, Harvard Medical School, Boston, MA, USA",
    "Neuro-oncology Department, Pitié-Salpétrière Hospital, Assistance Publique-Hôpitaux de Paris, Sorbonne Université, Paris, France",
    "Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA",
    "Harvard Medical School, Boston, MA, USA",
    "Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA",
    "Institute for Precision Medicine, University of Pittsburgh and UPMC, Pittsburgh, PA, USA",
    "Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA",
    "Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA",
    "UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, USA",
    "Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 69,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "James V. Neiswender",
      "orcid": "0000-0003-4135-6479"
    },
    {
      "affs": [
        0
      ],
      "name": "Samuel Maffa",
      "orcid": "0009-0008-8862-178X"
    },
    {
      "affs": [
        0
      ],
      "name": "Lisa Brenan",
      "orcid": "0009-0002-6131-062X"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Dina ElHarouni",
      "orcid": "0000-0003-1488-0347"
    },
    {
      "affs": [
        0
      ],
      "name": "Yejie Yun"
    },
    {
      "affs": [
        0
      ],
      "name": "Isabella Boyle",
      "orcid": "0000-0002-8138-1225"
    },
    {
      "affs": [
        0
      ],
      "name": "Kirsty Wienand",
      "orcid": "0000-0001-9548-4420"
    },
    {
      "affs": [
        0
      ],
      "name": "Haider Inam",
      "orcid": "0000-0003-3648-1857"
    },
    {
      "affs": [
        0
      ],
      "name": "Tate Bertea"
    },
    {
      "affs": [
        0
      ],
      "name": "Ashley Anderson",
      "orcid": "0000-0003-4004-8079"
    },
    {
      "affs": [
        0
      ],
      "name": "Megan Wong",
      "orcid": "0009-0000-4730-6232"
    },
    {
      "affs": [
        0
      ],
      "name": "Matias Enriquez"
    },
    {
      "affs": [
        0
      ],
      "name": "Evan Lenz",
      "orcid": "0009-0006-5271-4306"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Beatriz Villafranca-Magdalena",
      "orcid": "0000-0001-9921-919X"
    },
    {
      "affs": [
        0
      ],
      "name": "Nora Shanks"
    },
    {
      "affs": [
        0
      ],
      "name": "Mary Hager"
    },
    {
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        0
      ],
      "name": "Nia Lloyd",
      "orcid": "0009-0009-3019-5738"
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      ],
      "name": "Hannah Shadmany"
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      ],
      "name": "Sarah J. Wie",
      "orcid": "0000-0003-3042-7577"
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      ],
      "name": "Harry Liang"
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        0
      ],
      "name": "Konnor Yunghans",
      "orcid": "0009-0000-3834-8297"
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        0
      ],
      "name": "Xiaomeng Zhang",
      "orcid": "0000-0002-8536-6460"
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    {
      "affs": [
        0
      ],
      "name": "Lauren Golden"
    },
    {
      "affs": [
        0
      ],
      "name": "Hannah Harris"
    },
    {
      "affs": [
        0
      ],
      "name": "Serena Day"
    },
    {
      "affs": [
        0
      ],
      "name": "Philip G. Montgomery",
      "orcid": "0000-0002-2633-1081"
    },
    {
      "affs": [
        0
      ],
      "name": "Samantha Stokes"
    },
    {
      "affs": [
        1
      ],
      "name": "Ross M. Giglio",
      "orcid": "0000-0002-6208-8517"
    },
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        4,
        1
      ],
      "name": "Cynthia Hajal",
      "orcid": "0000-0002-0361-6703"
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        5,
        1,
        6
      ],
      "name": "James Richard Whittle",
      "orcid": "0000-0002-4740-2037"
    },
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        1
      ],
      "name": "Guadalupe Garcia",
      "orcid": "0000-0002-8673-2303"
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    {
      "affs": [
        7,
        8
      ],
      "name": "Caitlin E. Mills",
      "orcid": "0000-0002-2608-4084"
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        9
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      "name": "Mehdi Touat",
      "orcid": "0000-0002-5910-7799"
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        1
      ],
      "name": "Kristine Pelton",
      "orcid": "0000-0002-9066-4366"
    },
    {
      "affs": [
        1
      ],
      "name": "Hongyu Li",
      "orcid": "0000-0001-6525-9310"
    },
    {
      "affs": [
        1
      ],
      "name": "Prem Sai Prabhakar"
    },
    {
      "affs": [
        1
      ],
      "name": "Sonja Herter",
      "orcid": "0009-0007-9841-5085"
    },
    {
      "affs": [
        1
      ],
      "name": "Zoe Hoffmann Kamrat",
      "orcid": "0009-0001-5087-0587"
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    {
      "affs": [
        0,
        10
      ],
      "name": "Dan Y. Gui",
      "orcid": "0009-0003-9976-6435"
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    {
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        10,
        11
      ],
      "name": "Julien Dilly",
      "orcid": "0000-0002-4006-5285"
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    {
      "affs": [
        12
      ],
      "name": "Chen Khuan Wong",
      "orcid": "0000-0001-9811-3334"
    },
    {
      "affs": [
        0,
        10
      ],
      "name": "Jimmy A. Guo",
      "orcid": "0000-0002-4536-9640"
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        10
      ],
      "name": "Sangita Pal",
      "orcid": "0000-0002-4892-841X"
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    {
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        0,
        10
      ],
      "name": "Yossef Baidi",
      "orcid": "0000-0002-9289-5213"
    },
    {
      "affs": [
        0,
        10
      ],
      "name": "Ryan Johnston"
    },
    {
      "affs": [
        13
      ],
      "name": "Daniel D. Brown",
      "orcid": "0000-0002-7410-9514"
    },
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      ],
      "name": "Sonam Bhatia",
      "orcid": "0000-0002-0124-2621"
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      "name": "Peter S. Winter",
      "orcid": "0000-0002-6557-3219"
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      "name": "Srivatsan Raghavan",
      "orcid": "0000-0002-5374-9918"
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      "name": "Rameen Beroukhim",
      "orcid": "0000-0001-6303-3609"
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      ],
      "name": "Eva Colás",
      "orcid": "0000-0003-0302-4828"
    },
    {
      "affs": [
        14
      ],
      "name": "David L. Spector",
      "orcid": "0000-0003-3614-4965"
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      "name": "Adam Joel Bass",
      "orcid": "0000-0002-8193-4758"
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    {
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        7,
        8
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      "name": "Peter Karl Sorger",
      "orcid": "0000-0002-3364-1838"
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    {
      "affs": [
        15,
        12
      ],
      "name": "Yu Chen",
      "orcid": "0000-0002-0171-3884"
    },
    {
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        10,
        11
      ],
      "name": "Sarah J. Hill",
      "orcid": "0000-0002-9199-9459"
    },
    {
      "affs": [
        16
      ],
      "name": "Steffi Oesterreich",
      "orcid": "0000-0002-2537-6923"
    },
    {
      "affs": [
        13,
        16
      ],
      "name": "Adrian V. Lee",
      "orcid": "0000-0001-9917-514X"
    },
    {
      "affs": [
        10,
        11
      ],
      "name": "Himisha Beltran",
      "orcid": "0000-0003-3259-2226"
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      "name": "Jesse S. Boehm",
      "orcid": "0000-0002-6795-6336"
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  "bibtex": "https://research.draconitic.com/paper/a15dgr65mg4j2.bib",
  "cited_by": 8,
  "doi": "10.1038/s41586-026-10843-7",
  "fulltext_url": null,
  "id": "a15dgr65mg4j2",
  "issns": [
    "0028-0836",
    "1476-4687"
  ],
  "landing_url": "https://doi.org/10.1038/s41586-026-10843-7",
  "language": "en",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1306|Cancer Genomics and Diagnostics"
    ]
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  "openalex": "W7172493741",
  "pdf_url": null,
  "pmcid": "PMC13581591",
  "pmid": "42557315",
  "published": "2026-08-05",
  "publisher": "Nature Portfolio",
  "ris": "https://research.draconitic.com/paper/a15dgr65mg4j2.ris",
  "sources": [
    {
      "first_seen": "2026-11-04T13:21:07Z",
      "native_id": "W7172493741",
      "source": "openalex",
      "url": "https://doi.org/10.1038/s41586-026-10843-7"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:1306|Cancer Genomics and Diagnostics",
      "subfield": "oncology"
    }
  ],
  "title": "A dependency map enhanced with next-generation 3D cancer models",
  "title_text": "A dependency map enhanced with next-generation 3D cancer models",
  "type": "peer-reviewed",
  "updated_at": "2026-11-04T13:21:07Z",
  "url": "https://research.draconitic.com/paper/a15dgr65mg4j2",
  "venue": "Nature",
  "versions": []
}