{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T18:58:03Z","timestamp":1777316283531,"version":"3.51.4"},"reference-count":70,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2023,9,15]],"date-time":"2023-09-15T00:00:00Z","timestamp":1694736000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Department of Defense Neurofibromatosis Research Program (NFRP)","award":["W81XWH-17-1-0193"],"award-info":[{"award-number":["W81XWH-17-1-0193"]}]},{"name":"the Department of Defense Neurofibromatosis Research Program (NFRP)","award":["RF1 AG059088"],"award-info":[{"award-number":["RF1 AG059088"]}]},{"name":"NIH","award":["W81XWH-17-1-0193"],"award-info":[{"award-number":["W81XWH-17-1-0193"]}]},{"name":"NIH","award":["RF1 AG059088"],"award-info":[{"award-number":["RF1 AG059088"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Neurofibromatosis type 1 (Nf1) is a neurodevelopmental disorder and tumor syndrome caused by loss of function mutations in the neurofibromin gene (Nf1) and is estimated to affect 100,000 people in the US. Behavioral alterations and cognitive deficits have been found in 50\u201370% of children with Nf1 and include specific problems with attention, visual perception, language, learning, attention, and executive function. These behavioral alterations and cognitive deficits are observed in the absence of tumors or macroscopic structural abnormalities in the central nervous system. No effective treatments for the behavioral and cognitive disabilities of Nf1 exist. Inhibition of the anaplastic lymphoma kinase (Alk), a kinase which is negatively regulated by neurofibromin, allows for testing the hypothesis that this inhibition may be therapeutically beneficial in Nf1. In this review, we discuss this area of research and directions for the development of alternative therapeutic strategies to inhibit Alk. Even if the incidence of adverse reactions of currently available Alk inhibitors was reduced to half the dose, we anticipate that a long-term treatment would pose challenges for efficacy, safety, and tolerability. Therefore, future efforts are warranted to investigate alternative, potentially less toxic and more specific strategies to inhibit Alk function.<\/jats:p>","DOI":"10.3390\/cancers15184579","type":"journal-article","created":{"date-parts":[[2023,9,17]],"date-time":"2023-09-17T23:32:27Z","timestamp":1694993547000},"page":"4579","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Inhibition of Anaplastic Lymphoma Kinase (Alk) as Therapeutic Target to Improve Brain Function in Neurofibromatosis Type 1 (Nf1)"],"prefix":"10.3390","volume":"15","author":[{"given":"Joseph B.","family":"Weiss","sequence":"first","affiliation":[{"name":"Cardiovascular Institute and Warren Alpert School of Medicine at Brown University, Providence, RI 02840, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9861-9893","authenticated-orcid":false,"given":"Jacob","family":"Raber","sequence":"additional","affiliation":[{"name":"Departments of Behavioral Neuroscience, Neurology, and Radiation Medicine, Division of Neuroscience, ONPRC, Oregon Health & Science University, Portland, OR 97239, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"n71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 statement: An updated guideline for reporting systematic reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"704639","DOI":"10.3389\/fneur.2021.704639","article-title":"Impacts of NF1 Gene Mutations and Genetic Modifiers in Neurofibromatosis Type 1","volume":"12","author":"Wang","year":"2021","journal-title":"Front. 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