{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T17:00:14Z","timestamp":1788886814256,"version":"build-2803163510"},"reference-count":57,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2021,12,30]],"date-time":"2021-12-30T00:00:00Z","timestamp":1640822400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["MA2530\/8\u20101"],"award-info":[{"award-number":["MA2530\/8\u20101"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008672","name":"Wilhelm Sander-Stiftung","doi-asserted-by":"publisher","award":["2014.092.1"],"award-info":[{"award-number":["2014.092.1"]}],"id":[{"id":"10.13039\/100008672","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005972","name":"Deutsche Krebshilfe","doi-asserted-by":"publisher","award":["70112956"],"award-info":[{"award-number":["70112956"]}],"id":[{"id":"10.13039\/501100005972","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neuropathology Appl Neurobio"],"published-print":{"date-parts":[[2022,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>\n                      Meningiomas are the most frequent primary brain tumours. Recently, knowledge about the molecular drivers underlying aggressive meningiomas has been expanded. A hotspot mutation in the\n                      <jats:italic>AKT1<\/jats:italic>\n                      gene (\n                      <jats:italic>AKT1<\/jats:italic>\n                      <jats:sup>E17K<\/jats:sup>\n                      ), which is found in meningiomas at the convexity and especially at the skull base, has been associated with earlier tumour recurrence.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Here, we analysed the effects of the\n                      <jats:italic>AKT1<\/jats:italic>\n                      <jats:sup>E17K<\/jats:sup>\n                      mutation and treatment response to the Akt inhibitor AZD5363 in transgenic meningioma cell clones and mouse xenografts modelling convexity or skull base meningiomas.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We show that the\n                      <jats:italic>AKT<\/jats:italic>\n                      <jats:sup>E17K<\/jats:sup>\n                      mutation significantly enhances meningioma cell proliferation and colony size in vitro, resulting in significantly shortened survival times of mice carrying convexity or skull base\n                      <jats:italic>AKT1<\/jats:italic>\n                      <jats:sup>E17K<\/jats:sup>\n                      xenografts. Treatment of mutant cells or xenografts (150\u2009mg\/kg\/d) with AZD5363 revealed a significant decrease in cell proliferation and colony size and a prolongation of mouse survival. Western blots revealed activation of AKT1 kinase (phosphorylation at Ser273 and Thr308) by the E17K mutation in human meningioma samples and in our in vitro and in vivo models.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Our data suggest that\n                      <jats:italic>AKT1<\/jats:italic>\n                      <jats:sup>E17K<\/jats:sup>\n                      mutated meningiomas are a promising selective target for AZD5363.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/nan.12780","type":"journal-article","created":{"date-parts":[[2021,11,27]],"date-time":"2021-11-27T01:37:55Z","timestamp":1637977075000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["<i>AKT1<\/i>\n                    <sup>E17K<\/sup>\n                    \u2010mutated meningioma cell lines respond to treatment with the AKT inhibitor AZD5363"],"prefix":"10.1111","volume":"48","author":[{"given":"Peter","family":"John","sequence":"first","affiliation":[{"name":"Department of Neuropathology Otto von Guericke University  Magdeburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie","family":"Waldt","sequence":"additional","affiliation":[{"name":"Department of Neuropathology Otto von Guericke University  Magdeburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josephine","family":"Liebich","sequence":"additional","affiliation":[{"name":"Department of Neuropathology Otto von Guericke University  Magdeburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Kesseler","sequence":"additional","affiliation":[{"name":"Department of Neuropathology Otto von Guericke University  Magdeburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Schnabel","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Paracelsus Hospital Zwickau  Zwickau Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Angenstein","sequence":"additional","affiliation":[{"name":"Functional Imaging Group DZNE  Magdeburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I. Erol","family":"Sandalcioglu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Otto von Guericke University  Magdeburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cordula","family":"Scherlach","sequence":"additional","affiliation":[{"name":"Department of Neuroradiology University Hospital Leipzig  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5441-1962","authenticated-orcid":false,"given":"Felix","family":"Sahm","sequence":"additional","affiliation":[{"name":"Department of Neuropathology University Hospital Heidelberg  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elmar","family":"Kirches","sequence":"additional","affiliation":[{"name":"Department of Neuropathology Otto von Guericke University  Magdeburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6677-3124","authenticated-orcid":false,"given":"Christian","family":"Mawrin","sequence":"additional","affiliation":[{"name":"Department of Neuropathology Otto von Guericke University  Magdeburg 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