{
  "abstract": "Endocytosis regulates receptor trafficking and signaling, yet its role in colorectal cancer (CRC) remains unclear. We analyzed transcriptomic data from 15,025 CRC tumors to evaluate gene expression in clathrin-mediated endocytosis (CME) and the endosomal sorting complexes required for transport (ESCRT) pathway. Pathway-level signatures were compared across consensus molecular subtypes (CMS) and examined in relation to oncogenic signaling programs, while individual endocytosis-related genes were evaluated for associations with clinical outcomes in an independent randomized trial cohort. Expression of CME and ESCRT pathways varied by CMS, with the highest expression in CMS4 and the lowest in CMS3. Endocytosis signatures correlated with multiple oncogenic signaling pathways, including MAPK, TGF-β, WNT, PI3K, NOTCH, and angiogenesis, suggesting broad links between endocytic activity and tumor biology. In the randomized phase III CALGB/SWOG 80405 trial, low expression of AP2M1—a core adaptor in the CME complex—was significantly associated with longer overall survival and progression-free survival in patients treated with anti-EGFR agents, but not in those receiving anti-VEGF agents. These findings suggest that endocytic trafficking may be associated with oncogenic signaling and differential therapeutic benefit in patients with metastatic CRC. The endocytosis pathway reflects biologically relevant heterogeneity in CRC and may help guide therapeutic stratification.",
  "abstract_shown": true,
  "affiliations": [
    "Division of Medical Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA USA",
    "Department of Clinical Oncology, St. Marianna University School of Medicine, Kawasaki, Japan",
    "Clinical & Translational Research, Medical Affairs, Caris Life Sciences, Phoenix, AZ USA",
    "Department of Population and Public Health Sciences, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA USA",
    "Alliance Statistics and Data Management Center, Mayo Clinic, Rochester, MN USA",
    "UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC USA",
    "West Virginia University Cancer Institute, Morgantown, WV USA",
    "Department of Clinical Genetics, Fox Chase Cancer Center, Philadelphia, PA USA",
    "Division of hematology/oncology, University of Arizona Cancer Center, Tucson, AZ USA",
    "Department of Solid Tumor Oncology, GI Medical Oncology, Levine Cancer Institute, Charlotte, NC USA",
    "Division of Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis, MN USA",
    "Ruesch Center for the Cure of Gastrointestinal Cancers, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC USA",
    "Department of Medical Oncology, Rutgers Cancer Institute, New Brunswick, NJ USA",
    "University of California, San Francisco, San Francisco, CA USA"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 25,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Hiroyuki Arai",
      "orcid": "0000-0002-1886-7070"
    },
    {
      "affs": [
        2
      ],
      "name": "Andrew Elliott",
      "orcid": "0000-0001-8494-8031"
    },
    {
      "affs": [
        3
      ],
      "name": "Yan Yang",
      "orcid": "0000-0002-7883-0798"
    },
    {
      "affs": [
        2
      ],
      "name": "Alex Farrell"
    },
    {
      "affs": [
        3
      ],
      "name": "Joshua Millstein",
      "orcid": "0000-0001-7961-8943"
    },
    {
      "affs": [
        4
      ],
      "name": "Fang-Shu Ou",
      "orcid": "0000-0003-1267-8735"
    },
    {
      "affs": [
        5
      ],
      "name": "Federico Innocenti"
    },
    {
      "affs": [
        0
      ],
      "name": "Jingyuan Wang",
      "orcid": "0009-0006-6931-0359"
    },
    {
      "affs": [
        0
      ],
      "name": "Francesca Battaglin"
    },
    {
      "affs": [
        0
      ],
      "name": "Priya Jayachandran",
      "orcid": "0009-0002-2480-4057"
    },
    {
      "affs": [
        0
      ],
      "name": "Sandra Algaze"
    },
    {
      "affs": [
        0
      ],
      "name": "Shivani Soni"
    },
    {
      "affs": [
        0
      ],
      "name": "Wu Zhang"
    },
    {
      "affs": [
        6
      ],
      "name": "Richard M. Goldberg",
      "orcid": "0000-0003-0308-8223"
    },
    {
      "affs": [
        7
      ],
      "name": "Michael J. Hall"
    },
    {
      "affs": [
        8
      ],
      "name": "Aaron James Scott"
    },
    {
      "affs": [
        9
      ],
      "name": "Jimmy J. Hwang"
    },
    {
      "affs": [
        10
      ],
      "name": "Emil Lou",
      "orcid": "0000-0002-1607-1386"
    },
    {
      "affs": [
        11
      ],
      "name": "Benjamin A. Weinberg"
    },
    {
      "affs": [
        11
      ],
      "name": "John Marshall"
    },
    {
      "affs": [
        12
      ],
      "name": "Sanjay Goel",
      "orcid": "0000-0002-2798-7568"
    },
    {
      "affs": [
        2
      ],
      "name": "Joanne Xiu"
    },
    {
      "affs": [
        2
      ],
      "name": "W. Michael Korn"
    },
    {
      "affs": [
        13
      ],
      "name": "Alan P. Venook"
    },
    {
      "affs": [
        0
      ],
      "name": "Heinz-Josef Lenz",
      "orcid": "0000-0003-2178-9568"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/03aq394a4mjng.bib",
  "cited_by": 0,
  "doi": "10.1038/s41388-026-04019-w",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13723413/",
  "id": "03aq394a4mjng",
  "issns": [
    "0950-9232",
    "1476-5594"
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  "landing_url": "https://doi.org/10.1038/s41388-026-04019-w",
  "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",
      "Article"
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      "openalex",
      "2730|Colorectal Cancer Treatments and Studies"
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  "pdf_url": "https://www.nature.com/articles/s41388-026-04019-w.pdf",
  "pmcid": "PMC13723413",
  "pmid": "42897222",
  "published": "2026-10-19",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/03aq394a4mjng.ris",
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      "first_seen": "2026-11-04T12:22:03Z",
      "native_id": "PMC13723413",
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      "url": "https://doi.org/10.1038/s41388-026-04019-w"
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  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|Colorectal Cancer Treatments and Studies",
      "subfield": "oncology"
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  ],
  "title": "Activation of the endocytosis pathway stratifies subtypes and therapeutic sensitivity in colorectal cancer",
  "title_text": "Activation of the endocytosis pathway stratifies subtypes and therapeutic sensitivity in colorectal cancer",
  "type": "peer-reviewed",
  "updated_at": "2026-11-05T12:20:14Z",
  "url": "https://research.draconitic.com/paper/03aq394a4mjng",
  "venue": "Oncogene",
  "versions": []
}