{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T16:14:02Z","timestamp":1785600842796,"version":"3.56.0"},"reference-count":36,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2020,7,8]],"date-time":"2020-07-08T00:00:00Z","timestamp":1594166400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NCI K08","award":["5K08CA230179"],"award-info":[{"award-number":["5K08CA230179"]}]},{"name":"Children's Tumor Foundation DDI Award","award":["n\/a"],"award-info":[{"award-number":["n\/a"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Patients with RASopathy Neurofibromatosis 1 (NF1) are at a markedly increased risk of the development of benign and malignant tumors. Malignant tumors are often recalcitrant to treatments and associated with poor survival; however, no chemopreventative strategies currently exist. We thus evaluated the effect of mebendazole, alone or in combination with cyclooxygenase-2 (COX-2) inhibitors, on the prevention of NF1-related malignancies in a cis Nf1+\/\u2212;Tp53+\/\u2212 (NPcis) mouse model of NF1. Our in vitro findings showed that mebendazole (MBZ) inhibits the growth of NF1-related malignant peripheral nerve sheath tumors (MPNSTs) through a reduction in activated guanosine triphosphate (GTP)-bound Ras. The daily MBZ treatment of NPcis mice dosed at 195 mg\/kg daily, initiated 60 days after birth, substantially delayed the formation of solid malignancies and increased median survival (p &lt; 0.0001). Compared to placebo-treated mice, phosphorylated extracellular signal-regulated kinase (pERK) levels were decreased in the malignancies of MBZ-treated mice. The combination of MBZ with COX-2 inhibitor celecoxib (CXB) further enhanced the chemopreventative effect in female mice beyond each drug alone. These findings demonstrate the feasibility of a prevention strategy for malignancy development in high-risk NF1 individuals.<\/jats:p>","DOI":"10.3390\/genes11070762","type":"journal-article","created":{"date-parts":[[2020,7,10]],"date-time":"2020-07-10T09:45:31Z","timestamp":1594374331000},"page":"762","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Preventative Effect of Mebendazole against Malignancies in Neurofibromatosis 1"],"prefix":"10.3390","volume":"11","author":[{"given":"Verena","family":"Staedtke","sequence":"first","affiliation":[{"name":"Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tyler","family":"Gray-Bethke","sequence":"additional","affiliation":[{"name":"Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory J.","family":"Riggins","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren-Yuan","family":"Bai","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,7,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1111\/j.1749-6632.1986.tb48061.x","article-title":"The Genetic Aspects of Neurofibromatosis","volume":"486","author":"Carey","year":"1986","journal-title":"Ann. 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