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Adv."],"published-print":{"date-parts":[[2026,1,30]]},"abstract":"<jats:p>\n                    NF2 (neurofibromatosis type 2)\u2013related schwannomatosis (NF2-SWN) is a cancer predisposition syndrome characterized by the development of bilateral vestibular (VS) and spinal schwannomas. While benign, these tumors can cause substantial morbidity, and effective pharmacological treatments remain limited. Here, we demonstrate that genetic ablation of focal adhesion kinase (\n                    <jats:italic toggle=\"yes\">Fak\/Ptk2<\/jats:italic>\n                    ) impairs tumor formation and preserves hearing in a murine model of NF2. Mechanistically, we show that\n                    <jats:italic toggle=\"yes\">Fak<\/jats:italic>\n                    deletion decreases macrophage infiltration, attenuates nucleotide-binding oligomerization domain\u2013containing protein 2\u2013, leucine rich repeats (LRR)- and pyrin domain\u2013containing protein 3 inflammasome activation, and suppresses the hepatocyte growth factor\u2013MET axis. Pharmacological inhibition of FAK with single agent VS-4718 did not significantly reduce macroscopic tumor volume; however, its use in combination with the mitogen-activated protein kinase kinase (MEK) inhibitor selumetinib resulted in both a significant reduction in tumor volume and the preservation of dorsal root ganglion architecture. Our findings establish a critical role for FAK in schwannoma development and provide rationale for evaluation of combination FAK plus MEK inhibition in future clinical trials for NF2-associated SWN.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.ady8382","type":"journal-article","created":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T18:58:16Z","timestamp":1769799496000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":1,"title":["Inhibition of focal adhesion kinase impairs tumor formation and preserves hearing in a murine model of NF2-related schwannomatosis"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1022-1072","authenticated-orcid":true,"given":"Dana K.","family":"Mitchell","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kylee","family":"Brewster","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-6488-1927","authenticated-orcid":true,"given":"Li","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2496-1442","authenticated-orcid":true,"given":"Henry","family":"Mang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0685-9206","authenticated-orcid":true,"given":"Waylan K.","family":"Bessler","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaohong","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qingbo","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shaomin","family":"Qian","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric","family":"York","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6470-7142","authenticated-orcid":true,"given":"Sarah K.","family":"Morrow","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-5761-9918","authenticated-orcid":true,"given":"Shelley A. 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