{
  "abstract": "Introduction: Cancer-induced bone pain (CIBP) is a common symptom among patients with metastasized cancer, however, health professionals often face challenges in managing patients’ pain. Extracellular nicotinamide phosphoribosyltransferase (eNAMPT) is a DAMP overexpressed in metastatic breast carcinoma that binds to Toll-Like Receptor 4 (TLR4) to potentially trigger a signaling cascade through Nuclear Factor kappa β (NFk-β) inducing inflammation, osteoclastogenesis, and contributing to CIBP. To assess the impact of eNAMPT on CIBP and to identify alternative therapeutic options, ALT-100, an eNAMPT-neutralizing monoclonal antibody, was tested in murine and cell-based models.\n\nMethods: First, eNAMPT synthesis and secretion by EO771 breast adenocarcinoma cells and its modulation by ALT-100 were assessed using eNAMPT ELISA. Next, recombinant eNAMPT-induced osteoclastogenesis and its inhibition by ALT-100 were evaluated in RAW 264.7 osteoclast precursor cells using TRAP staining. In vivo, female C57BL/6J mice underwent intramedullary femoral injection of EO771 cells to establish CIBP or SHAM surgery. One week later, mice received ALT-100 (4 mg/kg, ip) or saline control, followed by longitudinal assessment of pain-related behaviors and femoral radiographs.\n\nResults: The eNAMPT ELISA assay revealed that EO771 cells synthesize and secrete eNAMPT in a time-dependent manner maximal at 48 h, which were reduced by ALT-100 mAb. In RAW 264.7 cells, recombinant eNAMPT significantly increased TRAP activity, while co-administration of ALT-100 significantly reduced this effect. In the murine CIBP model, ALT-100 significantly reduced pain-related behaviors compared to saline control mice in the cancer group. Moreover, radiographic analysis demonstrated that ALT-100 mitigates cancer-induced bone loss.\n\nDiscussion: These data show that ALT-100 exhibits antinociceptive effects in a CIBP murine model and inhibits eNAMPT-induced osteoclast differentiation. Our results indicate that blockade of eNAMPT can potentially serve as an alternative clinical strategy for treating CIBP.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Pharmacology, College of Medicine, University of Arizona, Tucson, AZ, United States",
    "The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology, University of Florida, Jupiter, FL, United States"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 12,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Nikhil C. Mathur"
    },
    {
      "affs": [
        0
      ],
      "name": "Ethan Villaroel"
    },
    {
      "affs": [
        0
      ],
      "name": "Isabella Villaroel"
    },
    {
      "affs": [
        0
      ],
      "name": "Erika Liktor-Busa"
    },
    {
      "affs": [
        0
      ],
      "name": "Kelly L. Karlage"
    },
    {
      "affs": [
        0
      ],
      "name": "Manvir Kaur"
    },
    {
      "affs": [
        1
      ],
      "name": "Carrie Kempf"
    },
    {
      "affs": [
        1
      ],
      "name": "Beatrice Gudaite"
    },
    {
      "affs": [
        1
      ],
      "name": "Zuo Ding"
    },
    {
      "affs": [
        1
      ],
      "name": "Joe G. N. Garcia"
    },
    {
      "affs": [
        0
      ],
      "name": "Tally M. Largent-Milnes"
    },
    {
      "affs": [
        0
      ],
      "name": "Todd W. Vanderah"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/21k3029q49f2g.bib",
  "cited_by": 0,
  "doi": "10.3389/fpain.2026.1955262",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13731207/",
  "id": "21k3029q49f2g",
  "issns": [
    "2673-561X"
  ],
  "landing_url": "https://doi.org/10.3389/fpain.2026.1955262",
  "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",
      "Original Research"
    ],
    [
      "openalex",
      "2730|Bone health and treatments"
    ]
  ],
  "openalex": "W7223123881",
  "pdf_url": "https://www.frontiersin.org/journals/pain-research/articles/10.3389/fpain.2026.1955262/pdf",
  "pmcid": "PMC13731207",
  "pmid": "42984933",
  "published": "2026-10-21",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/21k3029q49f2g.ris",
  "sources": [
    {
      "first_seen": "2026-11-08T12:21:26Z",
      "native_id": "PMC13731207",
      "source": "pmc",
      "url": "https://doi.org/10.3389/fpain.2026.1955262"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|Bone health and treatments",
      "subfield": "oncology"
    }
  ],
  "title": "A humanized eNAMPT -neutralizing monoclonal antibody reduces cancer-induced bone pain and osteoclastogenesis in murine breast cancer model",
  "title_text": "A humanized eNAMPT -neutralizing monoclonal antibody reduces cancer-induced bone pain and osteoclastogenesis in murine breast cancer model",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T12:21:26Z",
  "url": "https://research.draconitic.com/paper/21k3029q49f2g",
  "venue": "Frontiers in Pain Research",
  "versions": []
}