{
  "abstract": "Purpose of Review: Melanoma is a highly aggressive skin malignancy with increasing incidence and mortality worldwide. Among its key genetic alterations, NRAS mutations occur in approximately 15–25% of melanomas, defining a distinct molecular subset associated with aggressive tumor behavior and poor prognosis. Unlike BRAF mutations, NRAS alterations remain largely undruggable, posing significant therapeutic challenges. This review examines the histotype-specific distribution of NRAS mutations in melanoma and discusses their molecular and clinical implications.\n\nRecent Findings: Most NRAS mutations involve codon 61 and result in constitutive activation of the MAPK and PI3K signaling pathways, thereby promoting tumorigenesis and disease progression. Although NRAS-mutant melanomas are associated with an immunosuppressive tumor microenvironment, they also exhibit high immunogenicity, suggesting potential sensitivity to immune checkpoint inhibitors (ICIs). To further characterize the molecular landscape of NRAS-mutant melanoma, we analyzed data from the Catalogue of Somatic Mutations in Cancer (COSMIC), providing insights into the prevalence, distribution, co-mutation patterns, and functional consequences of NRAS alterations across different melanoma histotypes.\n\nSummary: NRAS mutations represent a major driver of melanoma progression and define a biologically and clinically distinct subset of the disease. Despite encouraging responses to immunotherapy, clinical outcomes remain suboptimal, highlighting the need for novel therapeutic approaches. A deeper understanding of NRAS-driven oncogenesis, histotype-specific mutation patterns, and their impact on therapeutic response is essential for advancing precision medicine and improving outcomes for patients with melanoma.",
  "abstract_shown": true,
  "affiliations": [
    "Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche, Traversa La Crucca 3, Sassari, 07100 Italy",
    "Istituto di Chimica Biomolecolare, Consiglio Nazionale delle Ricerche, Traversa La Crucca 3, Sassari, 07100 Italy",
    "Dipartimento di Medicina, Chirurgia e Farmacia, Università degli Studi di Sassari, Viale San Pietro 43, Sassari, 07100 Italy"
  ],
  "article_type": "review article",
  "arxiv": null,
  "author_total": 11,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Marina Pisano"
    },
    {
      "affs": [
        0
      ],
      "name": "Silvia Tore"
    },
    {
      "affs": [
        0
      ],
      "name": "Sara Demartis"
    },
    {
      "affs": [
        1
      ],
      "name": "Roberto Nico Dallocchio"
    },
    {
      "affs": [
        0
      ],
      "name": "Stefania Casula"
    },
    {
      "affs": [
        0
      ],
      "name": "Maria Colombino"
    },
    {
      "affs": [
        0
      ],
      "name": "Antonella Manca"
    },
    {
      "affs": [
        0
      ],
      "name": "Manuela Usai"
    },
    {
      "affs": [
        0
      ],
      "name": "Luca Nuvoli"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Giuseppe Palmieri"
    },
    {
      "affs": [
        0
      ],
      "name": "Milena Casula"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/0s06e6afc6cey.bib",
  "cited_by": 0,
  "doi": "10.1007/s11912-026-01851-x",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13710421/",
  "id": "0s06e6afc6cey",
  "issns": [
    "1523-3790",
    "1534-6269"
  ],
  "landing_url": "https://doi.org/10.1007/s11912-026-01851-x",
  "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",
      "Review"
    ],
    [
      "openalex",
      "1312|Melanoma and MAPK Pathways"
    ]
  ],
  "openalex": "W7223692378",
  "pdf_url": "https://link.springer.com/content/pdf/10.1007/s11912-026-01851-x.pdf",
  "pmcid": "PMC13710421",
  "pmid": "42931977",
  "published": "2026-10-26",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/0s06e6afc6cey.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T12:21:23Z",
      "native_id": "PMC13710421",
      "source": "pmc",
      "url": "https://doi.org/10.1007/s11912-026-01851-x"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Melanoma and MAPK Pathways",
      "subfield": "molecular-biology"
    }
  ],
  "title": "NRAS Mutations in Different Melanoma Histotypes: Molecular and Clinical Implications",
  "title_text": "NRAS Mutations in Different Melanoma Histotypes: Molecular and Clinical Implications",
  "type": "peer-reviewed",
  "updated_at": "2026-10-31T12:21:23Z",
  "url": "https://research.draconitic.com/paper/0s06e6afc6cey",
  "venue": "Current Oncology Reports",
  "versions": []
}