{
  "abstract": "Dysfunctional tumor vessels promote disease progression, whereas improved function enhances therapeutic delivery. However, current approaches to normalize tumor vasculature have limited efficacy. In vascular malformations, vessels are similarly dysfunctional, with endothelial cell (EC) hyperproliferation impairing arterial-venous specification. These defects are corrected with palbociclib, a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) that has beneficial effects on tumor and immune cells, but the effects on tumor vasculature are not well characterized. In our studies, murine mammary tumor ECs (TECs) exhibited disrupted cell cycle and specification, and CDK4/6i promoted TEC cycle control, enabling improved tumor vascular function. To investigate transcriptomic changes, we performed single-cell RNA sequencing (scRNA-seq) of treated and untreated tumors, and healthy tissues. CDK4/6i-mediated TEC cycle arrest promoted arterial-venous specification, cellular junctions, and pericyte association, and suppressed glycolytic and immunosuppressive gene expression. These effects were associated with increased vessel perfusion, decreased tumor hypoxia, and a more favorable immune landscape with immunotherapy. In scRNA-seq datasets from patients treated long-term with CDK4/6i, TECs exhibited similar transcriptomic changes associated with arterial-venous specification, pericyte recruitment, and immune signaling. Thus, in contrast to current strategies, CDK4/6i-mediated vascular changes may be maintained with continued treatment, highlighting the relevance of modulating TEC cycle to improve vessel maturation/function.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Cell Biology and",
    "Developmental Genomics Center",
    "Robert M. Berne Cardiovascular Research Center",
    "Comprehensive Cancer Center",
    "Departments of Molecular Physiology and Biophysics, and",
    "Biomedical Engineering, University of Virginia School of Medicine, Charlottesville, Virginia, USA.",
    "Department of Pediatrics, Division of Cardiology, University of Washington School of Medicine, Seattle, Washington, USA.",
    "Center for Developmental Biology and Regenerative Medicine, Seattle Children’s Research Institute, Seattle, Washington, USA.",
    "Radiology and Medical Imaging, and",
    "Microbiology, Immunology and Cancer Biology, University of Virginia School of Medicine, Charlottesville, Virginia, USA."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 14,
  "authors": [
    {
      "affs": [
        0,
        1,
        2,
        3
      ],
      "name": "Shelby R. Cain"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Gael Genet"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Nafiisha Genet"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Jordon W. Aragon"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Madeline G. Jackson"
    },
    {
      "affs": [
        2,
        4
      ],
      "name": "Victoria M. Milosek"
    },
    {
      "affs": [
        5
      ],
      "name": "Mark R. Schwartz"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Umadevi Paila"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Aleksandra Cwiek"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Zaneta Markowska"
    },
    {
      "affs": [
        6,
        7
      ],
      "name": "Nicholas W. Chavkin"
    },
    {
      "affs": [
        2,
        3,
        5,
        8
      ],
      "name": "Richard J. Price",
      "orcid": "0000-0002-0237-2102"
    },
    {
      "affs": [
        3,
        9
      ],
      "name": "Andrew C. Dudley"
    },
    {
      "affs": [
        0,
        1,
        2,
        3
      ],
      "name": "Karen K. Hirschi"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/91wegjhyg115y.bib",
  "cited_by": 0,
  "doi": "10.1172/jci.insight.203732",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13726565/",
  "id": "91wegjhyg115y",
  "issns": [
    "2379-3708"
  ],
  "landing_url": "https://doi.org/10.1172/jci.insight.203732",
  "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",
      "Research Article"
    ],
    [
      "openalex",
      "1312|Angiogenesis and VEGF in Cancer"
    ]
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  "openalex": "W7212148440",
  "pdf_url": "http://insight.jci.org/articles/view/203732/files/pdf",
  "pmcid": "PMC13726565",
  "pmid": "42720988",
  "published": "2026-09-10",
  "publisher": "American Society for Clinical Investigation",
  "ris": "https://research.draconitic.com/paper/91wegjhyg115y.ris",
  "sources": [
    {
      "first_seen": "2026-11-05T12:22:52Z",
      "native_id": "PMC13726565",
      "source": "pmc",
      "url": "https://doi.org/10.1172/jci.insight.203732"
    }
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  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Angiogenesis and VEGF in Cancer",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Endothelial cell cycle inhibition enables blood vessel maturation to normalize the tumor vasculature",
  "title_text": "Endothelial cell cycle inhibition enables blood vessel maturation to normalize the tumor vasculature",
  "type": "peer-reviewed",
  "updated_at": "2026-11-06T12:22:29Z",
  "url": "https://research.draconitic.com/paper/91wegjhyg115y",
  "venue": "JCI Insight",
  "versions": []
}