{
  "abstract": "Patient-derived glioblastoma (GBM) organoids (GBOs) maintain characteristics of their original tumors; however, they have not been widely applied to systematically assess therapy responses at scale or elucidate mechanisms underlying treatment resistance. Here, we develop a standardized reaggregated GBO (rGBO) platform for scalable, quantitative evaluation of radiation responses across 48 patients with GBM. Radiation responses in rGBOs correlate with the survival duration of corresponding patients treated with standard-of-care radiotherapy. Transcriptomic analyses identify gene signatures associated with radiosensitivity and radioresistance. Connectivity mapping with perturbational datasets identifies a panel of compounds with potential for reducing radioresistant and enhancing radiosensitive signatures. Subsequent testing demonstrates that inhibitors of bromodomain and extraterminal (BET) family proteins enhance radiotherapy efficacy in GBO and xenograft models by downregulating the radioresistant signature. Together, our study highlights the potential of rGBOs for standardizing therapeutic screening, evaluating patient-specific responses, identifying associated molecular features, and developing strategies to overcome treatment resistance.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Neuroscience and Mahoney Institute for Neurosciences, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA",
    "Neuroscience Graduate Group, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA",
    "Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA, USA",
    "Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA",
    "Department of Biology, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA, USA",
    "Program in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA",
    "Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA",
    "Glioblastoma Translational Center of Excellence, The Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA",
    "Division of Hematology and Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA",
    "Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA",
    "Parker Institute for Cancer Immunotherapy, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA",
    "Institute for Regenerative Medicine, University of Pennsylvania, Philadelphia, PA, USA",
    "Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA",
    "Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA",
    "The Epigenetics Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 24,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Xin Wang"
    },
    {
      "affs": [
        1
      ],
      "name": "Yusha Sun"
    },
    {
      "affs": [
        2
      ],
      "name": "Prithvi Sinha"
    },
    {
      "affs": [
        2
      ],
      "name": "Ruiying Su"
    },
    {
      "affs": [
        3
      ],
      "name": "Daniel Y. Zhang"
    },
    {
      "affs": [
        1
      ],
      "name": "Kristen H. Park"
    },
    {
      "affs": [
        4
      ],
      "name": "Yao Fu"
    },
    {
      "affs": [
        0
      ],
      "name": "Weifan Dong"
    },
    {
      "affs": [
        0
      ],
      "name": "Zhijian Zhang"
    },
    {
      "affs": [
        5
      ],
      "name": "Qing Wang"
    },
    {
      "affs": [
        5
      ],
      "name": "Daniel H. Geschwind"
    },
    {
      "affs": [
        5
      ],
      "name": "Riki Kawaguchi"
    },
    {
      "affs": [
        6
      ],
      "name": "Emily Ling-Lin Pai"
    },
    {
      "affs": [
        6
      ],
      "name": "Maria A. Gubbiotti"
    },
    {
      "affs": [
        6
      ],
      "name": "Robert Colbourn"
    },
    {
      "affs": [
        3
      ],
      "name": "Nduka M. Amankulor"
    },
    {
      "affs": [
        2,
        7
      ],
      "name": "Jay F. Dorsey"
    },
    {
      "affs": [
        6,
        7
      ],
      "name": "MacLean P. Nasrallah"
    },
    {
      "affs": [
        7,
        8
      ],
      "name": "Stephen J. Bagley"
    },
    {
      "affs": [
        3,
        7,
        9
      ],
      "name": "Zev A. Binder"
    },
    {
      "affs": [
        3,
        7,
        9,
        10
      ],
      "name": "Donald M. O’Rourke"
    },
    {
      "affs": [
        2,
        7
      ],
      "name": "Yi Fan"
    },
    {
      "affs": [
        0,
        11,
        12,
        13
      ],
      "name": "Guo-li Ming"
    },
    {
      "affs": [
        0,
        3,
        7,
        11,
        14
      ],
      "name": "Hongjun Song"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/d6fg4vhpg57hz.bib",
  "cited_by": 0,
  "doi": "10.1016/j.xcrm.2026.103095",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13710385/",
  "id": "d6fg4vhpg57hz",
  "issns": [
    "2666-3791"
  ],
  "landing_url": "https://doi.org/10.1016/j.xcrm.2026.103095",
  "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"
    ],
    [
      "openalex",
      "2716|Glioma Diagnosis and Treatment"
    ]
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  "openalex": "W7220845520",
  "pdf_url": null,
  "pmcid": "PMC13710385",
  "pmid": "42843344",
  "published": "2026-10-07",
  "publisher": "Elsevier",
  "ris": "https://research.draconitic.com/paper/d6fg4vhpg57hz.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T12:21:22Z",
      "native_id": "PMC13710385",
      "source": "pmc",
      "url": "https://doi.org/10.1016/j.xcrm.2026.103095"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2716|Glioma Diagnosis and Treatment",
      "subfield": "human-genetics"
    }
  ],
  "title": "A standardized patient-derived glioblastoma organoid platform for evaluating radiotherapy efficacy and overcoming resistance",
  "title_text": "A standardized patient-derived glioblastoma organoid platform for evaluating radiotherapy efficacy and overcoming resistance",
  "type": "peer-reviewed",
  "updated_at": "2026-10-31T12:21:22Z",
  "url": "https://research.draconitic.com/paper/d6fg4vhpg57hz",
  "venue": "Cell Reports Medicine",
  "versions": []
}