{
  "abstract": "Glioblastoma resists therapy through interconnected survival programs. Combined XPO1, Bcl-2, and Mcl-1 inhibition (Eltanexor, Venetoclax, A1210477; EVA) enhances the efficacy of chemotherapy, yet resistance persists. We hypothesized that PI3K/AKT/mTOR (PAM) signaling drives adaptive escape. TCGA/GTEx analyses and immunohistochemistry indicated PAM pathway activation in glioblastoma, with AKT significantly overexpressed, whereas PIK3CA showed a clear trend towards higher expression, although it did not reach statistical significance. qPCR analysis showed that PAM-component expression was highest in patient-derived glioblastoma stem-like cells (GSCs). In U87, U251, and GSCs, the dual PI3K/mTOR inhibitor Dactolisib combined with EVA and 5-Azacytidine reduced viability and induced apoptosis more effectively than any of the Rapamycin combinations, and the difference in apoptosis was most pronounced in U87 and GSCs. Dactolisib monotherapy shifted the cell cycle towards G1 with a reduced S-phase fraction. In CAM xenografts, [¹⁸F]FDG-PET/CT showed decreased tracer uptake, and Caspase-3 activation with PARP cleavage was detected only under EVA + Dactolisib treatment. Taken together, our results suggest that dual PI3K/mTOR inhibition with Dactolisib disables a critical adaptive survival axis, warranting further preclinical evaluation.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Hematology, Oncology & Immunology, Philipps-University Marburg, UKGM Marburg, Germany.",
    "Department of Neurosurgery, Philipps-University Marburg, UKGM Marburg, Germany.",
    "FACS Core Facility, Philipps-University Marburg, Germany.",
    "Department of Neuropathology, Philipps-University Marburg, UKGM Marburg, Germany.",
    "Core Facility Mouse Pathology and Electron Microscopy, Philipps-University Marburg, Germany.",
    "University Cancer Center (UCT) Frankfurt-Marburg, Germany.",
    "Dr. Senckenberg Institute of Neurooncology, Goethe-University Frankfurt, Germany.",
    "Department of Diagnostic and Interventional Radiology, Philipps-University Marburg, UKGM Marburg, Germany.",
    "Department of Nuclear Medicine, Philipps-University Marburg, UKGM Marburg, Germany."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 24,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Kai Zhao"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Leonie Meyer"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Madita Braun"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Katharina Otte"
    },
    {
      "affs": [
        1
      ],
      "name": "Celine Bitter"
    },
    {
      "affs": [
        1
      ],
      "name": "Maite Pawlik"
    },
    {
      "affs": [
        2
      ],
      "name": "Hartmann Raifer"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Frederik Helmprobst"
    },
    {
      "affs": [
        3,
        4,
        5
      ],
      "name": "Axel Pagenstecher"
    },
    {
      "affs": [
        5,
        6
      ],
      "name": "Hans Urban"
    },
    {
      "affs": [
        5,
        6
      ],
      "name": "Michael C Burger"
    },
    {
      "affs": [
        5,
        6
      ],
      "name": "Michael W Ronellenfitsch"
    },
    {
      "affs": [
        5,
        6
      ],
      "name": "Joachim P Steinbach"
    },
    {
      "affs": [
        7
      ],
      "name": "Jarmila Jedelská"
    },
    {
      "affs": [
        8
      ],
      "name": "Shamim Bagheri"
    },
    {
      "affs": [
        8
      ],
      "name": "Behrooz H Yousefi"
    },
    {
      "affs": [
        8
      ],
      "name": "Pietro Di Fazio",
      "orcid": "0000-0003-0091-8498"
    },
    {
      "affs": [
        8
      ],
      "name": "Markus Luster"
    },
    {
      "affs": [
        5,
        7
      ],
      "name": "Andreas H Mahnken"
    },
    {
      "affs": [
        0,
        5
      ],
      "name": "Andreas Neubauer"
    },
    {
      "affs": [
        0,
        5
      ],
      "name": "Andreas Burchert"
    },
    {
      "affs": [
        1,
        5
      ],
      "name": "Christopher Nimsky",
      "orcid": "0000-0002-8216-9410"
    },
    {
      "affs": [
        1,
        5
      ],
      "name": "Jörg W Bartsch",
      "orcid": "0000-0002-2773-3357"
    },
    {
      "affs": [
        0,
        5
      ],
      "name": "Tillmann Rusch",
      "orcid": "0009-0007-4848-5464"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/3qyeyz8ra5amb.bib",
  "cited_by": 0,
  "doi": "10.1002/2211-5463.70357",
  "fulltext_url": "https://europepmc.org/articles/PMC13695038",
  "id": "3qyeyz8ra5amb",
  "issns": [
    "2211-5463"
  ],
  "landing_url": "https://europepmc.org/article/MED/42920362",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|PI3K/AKT/mTOR signaling in cancer"
    ]
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  "openalex": "W7223472194",
  "pdf_url": "https://europepmc.org/articles/PMC13695038?pdf=render",
  "pmcid": "PMC13695038",
  "pmid": "42920362",
  "published": "2026-10-24",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/3qyeyz8ra5amb.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:33Z",
      "native_id": "MED:42920362",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42920362"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|PI3K/AKT/mTOR signaling in cancer",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Dactolisib outperforms Rapamycin in potentiating apoptosis induced by XPO1, Bcl-2 and Mcl-1 blockade in preclinical glioblastoma models.",
  "title_text": "Dactolisib outperforms Rapamycin in potentiating apoptosis induced by XPO1, Bcl-2 and Mcl-1 blockade in preclinical glioblastoma models.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:20:33Z",
  "url": "https://research.draconitic.com/paper/3qyeyz8ra5amb",
  "venue": "FEBS open bio",
  "versions": []
}