{
  "abstract": "Purpose:: Aspirin (Asa) and metformin (Met) have shown preventive efficacy in colorectal cancer. Preclinical data suggest convergence on NF-κB/PI3K–mTOR signaling and potential synergy. The ASAMET phase II trial tested this hypothesis in patients with resected stage I to III colorectal cancer.\n\nPatients and Methods:: In a 2 × 2 factorial, multicenter, double-blind study (EudraCT 2015-004824-77; NCT03047837), 51 patients were randomized to placebo, Asa 100 mg once daily, Met 850 mg twice daily, or AsaMet for 12 months. Biopsies of normal colonic mucosa and fasting blood samples were obtained at baseline and 12 months. NF-κB (primary endpoint), Ki67, EGFR, and pS6K were assessed by IHC.\n\nResults:: After 12 months, compared with placebo, Met reduced global NF-κB by −9.04 [95% confidence interval (CI), −17.55 to −0.54; P = 0.04], whereas Asa alone was inactive (−3.58; 95% CI, −12.15 to 4.99; P = 0.41), and AsaMet showed a nonsignificant reduction (−8.88; 95% CI, −18.86 to 1.10; P = 0.08). Pooled analyses confirmed a Met-driven effect (Met vs. non-Met: −7.29; 95% CI, −13.79 to −0.79; P = 0.03), with no impact of Asa (P = 0.73). Ki67 and pS6K were unchanged globally; however, AsaMet increased right-sided Ki67 (12.48; 95% CI, 0.45–24.51; P = 0.04). No treatment modulated pS6K. Toxicity was manageable, and no serious adverse events occurred.\n\nConclusions:: Met reduces NF-κB expression in normal colorectal mucosa of survivors of colorectal cancer, supporting its potential as a low-toxicity preventive agent. Asa did not favorably affect mucosal biomarkers. These findings support tissue-based endpoints and further evaluation of Met for colorectal cancer prevention.\n\nSignificance:: The ASAMET trial provides the first randomized evidence that Met significantly modulates NF-κB expression in histologically normal colorectal mucosa of survivors of colorectal cancer. This finding supports a biologically plausible mechanism of action in secondary cancer prevention that could be exploited in the postadjuvant setting. Asa, by contrast, did not favorably affect any mucosal biomarker endpoint in this population. These results may support a phase III study of Met in this setting.\n\nTrial Registration:: ClinicalTrials.gov Identifier: NCT03047837; EudraCT number: 2015-004824-77.",
  "abstract_shown": true,
  "affiliations": [
    "Division of Medical Oncology, E.O. Galliera Hospital, Genoa, Italy.",
    "Institute of Pathology, University Medical Centre, Mainz, Germany.",
    "Statistical Genetics Research Group, Institute of Medical Biometry, Heidelberg University, Heidelberg, Germany.",
    "Department of Clinical Pharmacology and Pharmacoepidemiology, Heidelberg University Hospital, Heidelberg, Germany.",
    "Division of Gastroenterology, E.O. Galliera Hospital, Genoa, Italy.",
    "Department of Gastroenterology, University Medical Centre Ljubljana, Ljubljana, Slovenia.",
    "Division of Visceral Surgery, Department of General Surgery, Medical University of Vienna, Vienna, Austria.",
    "Clinical and Epidemiological Research Unit, University Hospital of Parma, Parma, Italy.",
    "Huntsman Cancer Institute and Department of Population Health Sciences, University of Utah, Salt Lake City, Utah.",
    "Clinical Centre, Champalimaud Foundation, Lisbon, Portugal."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 22,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Irene M. Briata",
      "orcid": "0000-0003-0767-0026"
    },
    {
      "affs": [
        0
      ],
      "name": "Alessio Carbone",
      "orcid": "0009-0008-9907-3299"
    },
    {
      "affs": [
        1
      ],
      "name": "Sebastian Foersch",
      "orcid": "0000-0002-4740-6900"
    },
    {
      "affs": [
        1
      ],
      "name": "Katrin E. Tagscherer",
      "orcid": "0000-0002-0657-6399"
    },
    {
      "affs": [
        1
      ],
      "name": "Wilfried Roth",
      "orcid": "0000-0002-4847-9693"
    },
    {
      "affs": [
        2
      ],
      "name": "Dominique Scherer",
      "orcid": "0000-0003-4430-296X"
    },
    {
      "affs": [
        0
      ],
      "name": "Tania Buttiron Webber",
      "orcid": "0000-0002-3605-2828"
    },
    {
      "affs": [
        0
      ],
      "name": "Matteo Clavarezza",
      "orcid": "0000-0002-5053-1016"
    },
    {
      "affs": [
        3
      ],
      "name": "Jürgen Burhenne",
      "orcid": "0000-0002-2190-1698"
    },
    {
      "affs": [
        0
      ],
      "name": "Martino Oliva",
      "orcid": "0009-0004-5913-9258"
    },
    {
      "affs": [
        0
      ],
      "name": "Mauro D’Amico",
      "orcid": "0000-0001-5821-3410"
    },
    {
      "affs": [
        0
      ],
      "name": "Giorgia Giancarli",
      "orcid": "0009-0006-3155-2678"
    },
    {
      "affs": [
        4
      ],
      "name": "Massimo Oppezzi",
      "orcid": "0009-0002-1712-1784"
    },
    {
      "affs": [
        4
      ],
      "name": "Paola Romagnoli",
      "orcid": "0000-0001-9762-0967"
    },
    {
      "affs": [
        4
      ],
      "name": "Mauro Dalla Libera",
      "orcid": "0009-0005-5333-9854"
    },
    {
      "affs": [
        5
      ],
      "name": "Borut Stabuc",
      "orcid": "0000-0002-5281-4802"
    },
    {
      "affs": [
        6
      ],
      "name": "Thomas Bachleitner-Hofmann",
      "orcid": "0009-0004-3696-6015"
    },
    {
      "affs": [
        0
      ],
      "name": "Marilena Petrera",
      "orcid": "0009-0005-0414-7709"
    },
    {
      "affs": [
        0
      ],
      "name": "Laura Paleari",
      "orcid": "0000-0002-6176-2979"
    },
    {
      "affs": [
        7
      ],
      "name": "Matteo Puntoni",
      "orcid": "0000-0002-7908-0626"
    },
    {
      "affs": [
        8
      ],
      "name": "Cornelia M. Ulrich",
      "orcid": "0000-0001-7641-059X"
    },
    {
      "affs": [
        0,
        9
      ],
      "name": "Andrea DeCensi",
      "orcid": "0000-0003-2635-4491"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/87dkqybs598aa.bib",
  "cited_by": 0,
  "doi": "10.1158/2767-9764.crc-26-0556",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13732397/",
  "id": "87dkqybs598aa",
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  "landing_url": "https://doi.org/10.1158/2767-9764.crc-26-0556",
  "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",
      "Biological Mechanisms in Prevention"
    ],
    [
      "heading",
      "Biomarkers"
    ],
    [
      "heading",
      "Cancer Prevention"
    ],
    [
      "heading",
      "Cell Signaling"
    ],
    [
      "heading",
      "Clinical Trial Results"
    ],
    [
      "heading",
      "Colorectal Cancer"
    ],
    [
      "heading",
      "Gastrointestinal Cancers"
    ],
    [
      "heading",
      "Research Article"
    ],
    [
      "openalex",
      "1312|Metabolism, Diabetes, and Cancer"
    ]
  ],
  "openalex": "W7222918816",
  "pdf_url": "https://aacrjournals.org/cancerrescommun/article-pdf/doi/10.1158/2767-9764.CRC-26-0556/3840272/crc-26-0556.pdf",
  "pmcid": "PMC13732397",
  "pmid": "42895896",
  "published": "2026-11-04",
  "publisher": "American Association for Cancer Research",
  "ris": "https://research.draconitic.com/paper/87dkqybs598aa.ris",
  "sources": [
    {
      "first_seen": "2026-11-08T12:22:23Z",
      "native_id": "PMC13732397",
      "source": "pmc",
      "url": "https://doi.org/10.1158/2767-9764.crc-26-0556"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Metabolism, Diabetes, and Cancer",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Biomarker Modulation by Aspirin and Metformin for Colorectal Cancer Prevention: Results from the ASAMET Randomized Phase II Trial",
  "title_text": "Biomarker Modulation by Aspirin and Metformin for Colorectal Cancer Prevention: Results from the ASAMET Randomized Phase II Trial",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T12:22:23Z",
  "url": "https://research.draconitic.com/paper/87dkqybs598aa",
  "venue": "Cancer Research Communications",
  "versions": []
}