{
  "abstract": "Among molecular subtypes of glioblastoma (GBM), the mesenchymal subtype (MES) exhibits the most aggressive clinical course, marked by heightened invasiveness and therapeutic resistance. To overcome the challenge of intrinsic drug resistance in MES GBM, we performed a high-throughput screen of Food and Drug Administration (FDA)-approved compounds on NF1-silenced human GBM cells. We performed a high-throughput screen of 2,697 FDA-approved compounds on NF1-silenced human GBM cells, engineered via CRISPR/Cas9. This screen nominated poly(ADP-ribose) polymerase 1 (PARP1) inhibitors as top candidates, demonstrating selective cytotoxicity against NF1-deficient cells. Integrated analyses of The Cancer Genome Atlas (TCGA) data, immunofluorescence, and immunoblotting revealed significant PARP1 upregulation in GBM tissues, establishing its role as a proto-oncogene that drives tumor cell proliferation and migration. Using orthotopic xenograft models, we confirmed that NF1 knockdown (KD) profoundly sensitized GBM tumors to the anti-tumor and pro-apoptotic effects of PARP1 inhibition in vivo. Mechanistically, co-immunoprecipitation (co-IP) assays identified a physical interaction between the NF1 gene product neurofibromin and PARP1, suggesting a direct regulatory nexus. This study breaks through the traditional limitation of PARP inhibitors being used only for DNA repair defects, and for the first time reveals a novel selective killing mechanism of PARP1 inhibitors in NF1-deficient GBM. Collectively, our findings delineate NF1-mutant, MES GBM as a distinct clinical subset poised to derive therapeutic benefit from PARP1-targeted therapy.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Neurosurgery, The Second Hospital of Lanzhou University, Lanzhou, China.",
    "Gansu Provincial Clinical Research Center for Neurological Diseases, The Second Hospital of Lanzhou University, Lanzhou, China."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Hailin Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Qiao Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Xuan Yao"
    },
    {
      "affs": [
        0
      ],
      "name": "Bo Wang"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Yawen Pan",
      "orcid": "0009-0009-9536-386X"
    },
    {
      "affs": [
        1
      ],
      "name": "Guoqiang Yuan",
      "orcid": "0000-0003-4945-5535"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/5evy6dywm9907.bib",
  "cited_by": 0,
  "doi": "10.21037/tcr-2026-1700",
  "fulltext_url": "https://europepmc.org/articles/PMC13743360",
  "id": "5evy6dywm9907",
  "issns": [
    "2218-676X",
    "2219-6803"
  ],
  "landing_url": "https://europepmc.org/article/MED/42999379",
  "language": "eng",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2730|PARP inhibition in cancer therapy"
    ]
  ],
  "openalex": "W7224118817",
  "pdf_url": "https://europepmc.org/articles/PMC13743360?pdf=render",
  "pmcid": "PMC13743360",
  "pmid": "42999379",
  "published": "2026-10-26",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/5evy6dywm9907.ris",
  "sources": [
    {
      "first_seen": "2026-11-09T15:20:34Z",
      "native_id": "MED:42999379",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42999379"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2730|PARP inhibition in cancer therapy",
      "subfield": "oncology"
    }
  ],
  "title": "Inhibition of malignant progression in mesenchymal glioblastoma by PARP1 inhibitors.",
  "title_text": "Inhibition of malignant progression in mesenchymal glioblastoma by PARP1 inhibitors.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T15:20:34Z",
  "url": "https://research.draconitic.com/paper/5evy6dywm9907",
  "venue": "Translational cancer research",
  "versions": []
}