{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T11:08:21Z","timestamp":1778843301735,"version":"3.51.4"},"reference-count":11,"publisher":"SAGE Publications","issue":"6","license":[{"start":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T00:00:00Z","timestamp":1773100800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"National Cancer Institute","award":["CA240601"],"award-info":[{"award-number":["CA240601"]}]},{"name":"National Cancer Institute","award":["CA269594"],"award-info":[{"award-number":["CA269594"]}]},{"DOI":"10.13039\/100008222","name":"Ben and Catherine Ivy Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100008222","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["DNA and Cell Biology"],"published-print":{"date-parts":[[2026,6,1]]},"abstract":"\n Glioblastoma multiforme (GBM) is the most prevalent and aggressive malignant primary brain tumor, marked by rapid growth, extensive invasiveness, and a median survival of only \u223c15 months despite current multimodal therapy. To identify new therapeutic vulnerabilities, we investigated the actin-regulatory protein\n AVIL<\/jats:italic>\n , previously implicated through a\n MARS-AVIL<\/jats:italic>\n gene fusion in rhabdomyosarcoma. Comprehensive genomic and transcriptomic analyses across REMBRANDT, TCGA, and CGGA datasets revealed recurrent\n AVIL<\/jats:italic>\n amplification and consistently elevated AVIL expression in GBM compared with normal brain tissue.\n AVIL<\/jats:italic>\n was overexpressed across all GBM molecular subtypes and glioma stem cell (GSC) states but was nearly undetectable in normal astrocytes, neural stem cells, and brain tissues. Functional studies demonstrated that\n AVIL<\/jats:italic>\n is both necessary and sufficient for glioma genesis:\n AVIL<\/jats:italic>\n silencing eradicated GBM cells\n in vitro<\/jats:italic>\n and suppressed xenograft growth\n in\u00a0vivo<\/jats:italic>\n , while\n AVIL<\/jats:italic>\n overexpression enhanced proliferation, migration, and transformation. Mechanistically,\n AVIL<\/jats:italic>\n drives tumor progression through actin cytoskeleton remodeling and activation of the FOXM1-LIN28B oncogenic pathway. Using a small molecule microarray screen, we identified a selective\n AVIL<\/jats:italic>\n -binding compound (compound A) that potently inhibited GBM cell growth with minimal toxicity to normal astrocytes. Gene expression changes induced by compound A mirrored those following\n AVIL<\/jats:italic>\n knockdown, indicating on-target activity. Compound A demonstrated robust antitumor efficacy in multiple preclinical GBM models, including orthotopic xenografts, GSC-derived tumors, patient-derived xenografts, and temozolomide-resistant GBM with favorable pharmacokinetics and blood\u2013brain barrier penetration. The minimal\n AVIL<\/jats:italic>\n expression in normal tissues and lack of phenotype in\n AVIL<\/jats:italic>\n -deficient mice underscore its potential as a low-toxicity therapeutic target. Together, these findings establish\n AVIL<\/jats:italic>\n as a critical oncogenic driver in GBM and introduce a first-in-class\n AVIL<\/jats:italic>\n inhibitor with strong translational promise for precision neuro-oncology.\n <\/jats:p>","DOI":"10.1177\/10445498261431994","type":"journal-article","created":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T18:27:31Z","timestamp":1773253651000},"page":"263-266","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["First-in-Class Small Molecule Inhibitor of Oncogene\n AVIL<\/i>\n in Glioblastoma"],"prefix":"10.1177","volume":"45","author":[{"given":"Zhongqiu","family":"Xie","sequence":"first","affiliation":[{"name":"Department of Pathology, School of Medicine, University of Virginia, Charlottesville, Virginia, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sophia","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Medicine, University of Virginia, Charlottesville, Virginia, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7879-1792","authenticated-orcid":false,"given":"Hui","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Medicine, University of Virginia, Charlottesville, Virginia, USA."},{"name":"Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, Virginia, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2026,3,10]]},"reference":[{"key":"e_1_3_3_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2006.282"},{"key":"e_1_3_3_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-07767-5"},{"key":"e_1_3_3_4_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2023.0023"},{"key":"e_1_3_3_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2023.02.002"},{"key":"e_1_3_3_6_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1612734113"},{"key":"e_1_3_3_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-17279-1"},{"key":"e_1_3_3_8_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.adt1211"},{"key":"e_1_3_3_9_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2118048119"},{"key":"e_1_3_3_10_1","doi-asserted-by":"publisher","DOI":"10.1080\/23723556.2020.1804309"},{"key":"e_1_3_3_11_1","doi-asserted-by":"publisher","DOI":"10.1080\/23723556.2016.1263714"},{"key":"e_1_3_3_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-025-08591-1"}],"container-title":["DNA and Cell Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/10445498261431994","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/10445498261431994","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/10445498261431994","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T10:20:56Z","timestamp":1778840456000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/10445498261431994"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,10]]},"references-count":11,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,6,1]]}},"alternative-id":["10.1177\/10445498261431994"],"URL":"https:\/\/doi.org\/10.1177\/10445498261431994","relation":{},"ISSN":["1044-5498","1557-7430"],"issn-type":[{"value":"1044-5498","type":"print"},{"value":"1557-7430","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,10]]}}}