{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T18:24:32Z","timestamp":1793903072202,"version":"4.8.0"},"reference-count":64,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T00:00:00Z","timestamp":1791590400000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Else Kr\u00f6ner Fresenius Stiftung"},{"name":"Doctoral Scholarship Programs of the Medical Faculty T\u00fcbingen"},{"name":"Deutsche Gesellschaft f\u00fcr H\u00e4matologie und Medizinische Onkologie","id":[{"id":"https:\/\/ror.org\/023avht41","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Deutsche Gesellschaft f\u00fcr Innere Medizin, Clinican Scientist"},{"name":"MINT-Clinician Scientist Program of the Medical Faculty T\u00fcbingen"},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["493665037"],"award-info":[{"award-number":["493665037"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Therapeutic options for progressive glioblastoma remain limited, with chlorethyl-cyclohexyl-nitrosourea (CCNU, lomustine) among the approved treatments. Beyond MGMT gene promoter methylation, molecular determinants of CCNU sensitivity or resistance are ill-defined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We employed genome-wide functional knockout screening using the CRISPR-Cas9 technology to identify and subsequently validate modulators of response to CCNU in experimental glioma. We established an immunocompetent glioma mouse model to enable functional interrogation of Fanconi anemia pathway (FA) genes in tumor growth and synthetic lethal interactions in vivo using the RCAS\/tv-a somatic gene delivery system.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Multiple FA pathway members recurrently emerged as potent synthetic lethal interactors of CCNU treatment. In vivo knockdown of FANCM accelerated tumor onset and significantly increased CCNU sensitivity. Consistently, FA pathway inhibition enhanced CCNU efficacy across in vitro, ex vivo and in vivo models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Together, these findings identify FA pathway components as key synthetic lethal interactors of CCNU response and reveal a therapeutically actionable vulnerability in glioblastoma.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/neuonc\/noag254","type":"journal-article","created":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T11:48:46Z","timestamp":1791632926000},"source":"Crossref","is-referenced-by-count":0,"title":["Fanconi anemia pathway disruption drives lomustine sensitivity in glioma"],"prefix":"10.1093","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0306-1143","authenticated-orcid":false,"given":"Hannes","family":"Becker","sequence":"first","affiliation":[{"name":"Department of Neurology & Interdisciplinary Neuro-Oncology, University Hospital T\u00fcbingen, Hertie Institute for Clinical Brain Research, Eberhard Karls University T\u00fcbingen , T\u00fcbingen,","place":["Germany"]},{"name":"Cluster of Excellence (EXC 2180) \u201cImage Guided and Functionally Instructed Tumor Therapies\u201d, Eberhard Karls University of T\u00fcbingen , T\u00fcbingen,","place":["Germany"]},{"name":"Department of Neurosurgery, University Hospital T\u00fcbingen, Eberhard Karls University T\u00fcbingen , T\u00fcbingen,","place":["Germany"]},{"name":"Center for Neuro-Oncology, Comprehensive Cancer Center T\u00fcbingen-Stuttgart, Eberhard Karls University T\u00fcbingen , T\u00fcbingen,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9734-4843","authenticated-orcid":false,"given":"Bianca","family":"Walter","sequence":"additional","affiliation":[{"name":"Department of Neurology & Interdisciplinary Neuro-Oncology, University Hospital T\u00fcbingen, Hertie Institute for Clinical Brain Research, Eberhard Karls University T\u00fcbingen , T\u00fcbingen,","place":["Germany"]},{"name":"Cluster of Excellence (EXC 2180) \u201cImage Guided and Functionally Instructed Tumor Therapies\u201d, Eberhard Karls University of T\u00fcbingen , T\u00fcbingen,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3288-4280","authenticated-orcid":false,"given":"Lara Annina","family":"Haeusser","sequence":"additional","affiliation":[{"name":"Department of Neurology & Interdisciplinary Neuro-Oncology, University Hospital T\u00fcbingen, Hertie Institute for Clinical Brain Research, Eberhard Karls University T\u00fcbingen , T\u00fcbingen,","place":["Germany"]},{"name":"Cluster of Excellence (EXC 2180) \u201cImage Guided and Functionally Instructed Tumor Therapies\u201d, Eberhard Karls University of T\u00fcbingen , T\u00fcbingen,","place":["Germany"]},{"name":"German 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for Clinical Brain Research, Eberhard Karls University T\u00fcbingen , T\u00fcbingen,","place":["Germany"]},{"name":"Cluster of Excellence (EXC 2180) \u201cImage Guided and Functionally Instructed Tumor Therapies\u201d, Eberhard Karls University of T\u00fcbingen , T\u00fcbingen,","place":["Germany"]},{"name":"M3 Research Center for Malignome, Metabolome and Microbiome, Faculty of Medicine, Eberhard Karls University T\u00fcbingen , T\u00fcbingen,","place":["Germany"]},{"name":"Institute of Biomedical Informatics, University Hospital T\u00fcbingen, Eberhard Karls University T\u00fcbingen , T\u00fcbingen,","place":["Germany"]},{"name":"Department of Computer Science, Eberhard Karls University T\u00fcbingen , T\u00fcbingen,","place":["Germany"]},{"name":"Department of Internal Medicine I, University Hospital T\u00fcbingen , 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