{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T07:38:30Z","timestamp":1792827510240,"version":"4.5.0"},"reference-count":81,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:00:00Z","timestamp":1792800000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:00:00Z","timestamp":1792800000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"publisher","award":["01KU2503"],"award-info":[{"award-number":["01KU2503"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009560","name":"Uniklinikum Giessen und Marburg","doi-asserted-by":"publisher","award":["11\/2023MR"],"award-info":[{"award-number":["11\/2023MR"]}],"id":[{"id":"10.13039\/501100009560","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["FEBS Open Bio"],"abstract":"<jats:p>\n                    Glioblastoma resists therapy through interconnected survival programs. Combined XPO1, Bcl\u20102, and Mcl\u20101 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\u2010component expression was highest in patient\u2010derived glioblastoma stem\u2010like cells (GSCs). In U87, U251, and GSCs, the dual PI3K\/mTOR inhibitor Dactolisib combined with EVA and 5\u2010Azacytidine 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\u2010phase fraction. In CAM xenografts, [\n                    <jats:sup>18<\/jats:sup>\n                    F]FDG\u2010PET\/CT showed decreased tracer uptake, and Caspase\u20103 activation with PARP cleavage was detected only under EVA\u2009+\u2009Dactolisib treatment. Taken together, our results suggest that dual PI3K\/mTOR inhibition with Dactolisib disables a critical adaptive survival axis, warranting further preclinical evaluation.\n                  <\/jats:p>","DOI":"10.1002\/2211-5463.70357","type":"journal-article","created":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T07:25:41Z","timestamp":1792826741000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dactolisib outperforms Rapamycin in potentiating apoptosis induced by\n                    <scp>XPO1<\/scp>\n                    , Bcl\u20102\u00a0and Mcl\u20101 blockade in preclinical glioblastoma models"],"prefix":"10.1002","author":[{"given":"Kai","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Hematology, Oncology &amp; Immunology Philipps\u2010University Marburg, UKGM Marburg  Germany"},{"name":"Department of Neurosurgery Philipps\u2010University Marburg, UKGM Marburg  Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonie","family":"Meyer","sequence":"additional","affiliation":[{"name":"Department of Hematology, Oncology &amp; Immunology Philipps\u2010University Marburg, UKGM Marburg  Germany"},{"name":"Department of Neurosurgery Philipps\u2010University Marburg, UKGM Marburg  Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madita","family":"Braun","sequence":"additional","affiliation":[{"name":"Department of Hematology, Oncology &amp; Immunology Philipps\u2010University Marburg, UKGM Marburg  Germany"},{"name":"Department of Neurosurgery Philipps\u2010University Marburg, UKGM Marburg  Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina","family":"Otte","sequence":"additional","affiliation":[{"name":"Department of Hematology, Oncology &amp; Immunology Philipps\u2010University Marburg, UKGM Marburg  Germany"},{"name":"Department of Neurosurgery Philipps\u2010University 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Marburg  Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Axel","family":"Pagenstecher","sequence":"additional","affiliation":[{"name":"Department of Neuropathology Philipps\u2010University Marburg, UKGM Marburg  Germany"},{"name":"Core Facility Mouse Pathology and Electron Microscopy Philipps\u2010University Marburg  Germany"},{"name":"University Cancer Center (UCT) Frankfurt\u2010Marburg  Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans","family":"Urban","sequence":"additional","affiliation":[{"name":"University Cancer Center (UCT) Frankfurt\u2010Marburg  Germany"},{"name":"Dr. Senckenberg Institute of Neurooncology Goethe\u2010University Frankfurt  Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael C.","family":"Burger","sequence":"additional","affiliation":[{"name":"University Cancer Center (UCT) Frankfurt\u2010Marburg  Germany"},{"name":"Dr. Senckenberg Institute of Neurooncology Goethe\u2010University Frankfurt  Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael W.","family":"Ronellenfitsch","sequence":"additional","affiliation":[{"name":"University Cancer Center (UCT) Frankfurt\u2010Marburg  Germany"},{"name":"Dr. Senckenberg Institute of Neurooncology Goethe\u2010University Frankfurt  Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joachim P.","family":"Steinbach","sequence":"additional","affiliation":[{"name":"University Cancer Center (UCT) Frankfurt\u2010Marburg  Germany"},{"name":"Dr. Senckenberg Institute of Neurooncology Goethe\u2010University Frankfurt  Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jarmila","family":"Jedelsk\u00e1","sequence":"additional","affiliation":[{"name":"Department of Diagnostic and Interventional Radiology Philipps\u2010University Marburg, UKGM Marburg  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