{
  "abstract": "Immune checkpoint inhibitors (ICIs) and BRAF/MEK kinase inhibitors have substantially improved survival in advanced melanoma; however, therapeutic resistance and severe toxicities underscore the ongoing need for alternative strategies. Here, we evaluate the clinical utility of multi-omic profiling, biomarker-stratified recommendations, and survival outcomes within a prospective cohort of 98 patients with advanced cutaneous or uveal melanoma evaluated by the Molecular Tumor Board Freiburg (MTB-FR) between 2021 and 2024. Completed profiling revealed at least one potential actionable target beyond classical BRAF V600 mutations in 83.8% of cases. Alterations in NRAS, atypical BRAF variants, CDK4/6 pathway amplifications, and DNA-damage response (DDR) gene mutations most frequently guided board recommendations. Biomarker-stratified therapies were recommended for 68.4% of patients, and personalized immunotherapy combinations for 72.4%. The treatment implementation rate was 33.8% (n = 27), achieving an overall disease control rate (DCR) of 42.9% and an overall response rate (ORR) of 10.7%. These findings demonstrate that comprehensive molecular profiling in a real-world setting uncovers actionable alterations, providing viable subsequent treatment avenues that may optimize outcomes for heavily pretreated melanoma patients beyond established standards of care. Ultimately, prospective, randomized, biomarker-driven trials remain essential to validate whether these individualized diagnostic strategies translate into a reproducible survival benefit.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Medicine I-Medical Centre-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.",
    "Comprehensive Cancer Center Freiburg, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.",
    "Institute of Medical Bioinformatics and Systems Medicine (IBSM), Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.",
    "German Cancer Consortium (DKTK), Partner Site Freiburg, a partnership between DKFZ and Medical Center-University of Freiburg, Freiburg, Germany.",
    "Institute of Molecular Medicine and Cell Research (IMMZ), Faculty of Medicine, University of Freiburg, Freiburg, Germany.",
    "Institute for Surgical Pathology, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.",
    "Department of Dermatology and Venereology-Medical Centre-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.",
    "Department of Hematology and Medical Oncology, University Medical Center Göttingen, Göttingen, Germany.",
    "Department of Medicine III, Faculty of Medicine, Klinikum Rechts der Isar, Technical University Munich (TUM), Munich, Germany.",
    "Center of Personalized Medicine, Technical University of Munich (TUM), University Hospital, Technical University of Munich, Munich, Germany.",
    "Department of Dermatology and Venereology-Medical Centre-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany. david.rafei-shamsabadi@uniklinik-freiburg.de."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 33,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "T Lowinus"
    },
    {
      "affs": [
        2
      ],
      "name": "V Schipperges"
    },
    {
      "affs": [
        2
      ],
      "name": "P Metzger",
      "orcid": "0000-0002-2451-1943"
    },
    {
      "affs": [
        1,
        3,
        4
      ],
      "name": "T Brummer"
    },
    {
      "affs": [
        5
      ],
      "name": "U Matysiak"
    },
    {
      "affs": [
        1,
        5
      ],
      "name": "E P Dopfer"
    },
    {
      "affs": [
        2
      ],
      "name": "M E Hess"
    },
    {
      "affs": [
        4,
        5
      ],
      "name": "M Fahrner"
    },
    {
      "affs": [
        2
      ],
      "name": "T Pauli"
    },
    {
      "affs": [
        2
      ],
      "name": "A Blaumeiser",
      "orcid": "0009-0001-5621-0424"
    },
    {
      "affs": [
        0,
        1,
        3
      ],
      "name": "H Becker",
      "orcid": "0000-0002-6919-4048"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "J Kuehn",
      "orcid": "0000-0002-0400-6050"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "M Rassner"
    },
    {
      "affs": [
        0
      ],
      "name": "J Falkenstein"
    },
    {
      "affs": [
        0
      ],
      "name": "H Bertemes"
    },
    {
      "affs": [
        0
      ],
      "name": "P Bovio",
      "orcid": "0000-0002-3203-9984"
    },
    {
      "affs": [
        5
      ],
      "name": "N Pinter",
      "orcid": "0000-0002-8241-6821"
    },
    {
      "affs": [
        1,
        5
      ],
      "name": "S Cysar"
    },
    {
      "affs": [
        6
      ],
      "name": "S Lehr"
    },
    {
      "affs": [
        0
      ],
      "name": "R Wäsch",
      "orcid": "0000-0002-0813-3444"
    },
    {
      "affs": [
        0,
        1,
        3,
        7
      ],
      "name": "L Gräßel"
    },
    {
      "affs": [
        6
      ],
      "name": "K Eyerich",
      "orcid": "0000-0003-0094-2674"
    },
    {
      "affs": [
        1,
        3,
        5
      ],
      "name": "A M Schultheis"
    },
    {
      "affs": [
        1,
        3,
        5
      ],
      "name": "O Schilling"
    },
    {
      "affs": [
        1,
        3,
        5
      ],
      "name": "S Lassmann"
    },
    {
      "affs": [
        1,
        3,
        5
      ],
      "name": "M Werner"
    },
    {
      "affs": [
        0,
        7,
        8,
        9
      ],
      "name": "A L Illert"
    },
    {
      "affs": [
        0,
        1,
        3
      ],
      "name": "J Duyster"
    },
    {
      "affs": [
        0,
        1,
        3
      ],
      "name": "R Zeiser",
      "orcid": "0000-0001-6565-3393"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "C C Miething",
      "orcid": "0000-0003-4699-3805"
    },
    {
      "affs": [
        1,
        2,
        3
      ],
      "name": "M Boerries",
      "orcid": "0000-0002-3670-0602"
    },
    {
      "affs": [
        6
      ],
      "name": "F Meiss",
      "orcid": "0000-0002-4044-9094"
    },
    {
      "affs": [
        10
      ],
      "name": "D Rafei"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/4ayh8t2vaakmr.bib",
  "cited_by": 0,
  "doi": "10.1038/s41698-026-01763-w",
  "fulltext_url": "https://europepmc.org/articles/PMC13687070",
  "id": "4ayh8t2vaakmr",
  "issns": [
    "2397-768X"
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  "landing_url": "https://europepmc.org/article/MED/42907470",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "lcc",
      "RC254-282"
    ],
    [
      "openalex",
      "1312|Melanoma and MAPK Pathways"
    ]
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  "openalex": "W7223143037",
  "pdf_url": "https://europepmc.org/articles/PMC13687070?pdf=render",
  "pmcid": "PMC13687070",
  "pmid": "42907470",
  "published": "2026-10-21",
  "publisher": "Nature Portfolio",
  "ris": "https://research.draconitic.com/paper/4ayh8t2vaakmr.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:53Z",
      "native_id": "MED:42907470",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42907470"
    },
    {
      "first_seen": "2026-10-30T13:45:34Z",
      "native_id": "727dff9a00e5449facae682136f7cc5d",
      "source": "doaj",
      "url": "https://doi.org/10.1038/s41698-026-01763-w"
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  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Melanoma and MAPK Pathways",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Precision oncology in advanced melanoma: molecular landscapes and personalized therapy recommendations from the Molecular Tumor Board Freiburg.",
  "title_text": "Precision oncology in advanced melanoma: molecular landscapes and personalized therapy recommendations from the Molecular Tumor Board Freiburg.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T13:45:34Z",
  "url": "https://research.draconitic.com/paper/4ayh8t2vaakmr",
  "venue": "NPJ precision oncology",
  "versions": []
}