{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T00:08:30Z","timestamp":1793405310749,"version":"4.5.0"},"reference-count":37,"publisher":"Elsevier BV","issue":"2","license":[{"start":{"date-parts":[[2023,5,1]],"date-time":"2023-05-01T00:00:00Z","timestamp":1682899200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2023,5,1]],"date-time":"2023-05-01T00:00:00Z","timestamp":1682899200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"content-domain":{"domain":["jpet.aspetjournals.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pharmacology and Experimental Therapeutics"],"published-print":{"date-parts":[[2023,5]]},"DOI":"10.1124\/jpet.122.001431","type":"journal-article","created":{"date-parts":[[2023,2,27]],"date-time":"2023-02-27T22:57:42Z","timestamp":1677538662000},"page":"106-116","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":16,"title":["Combining SOS1 and MEK Inhibitors in a Murine Model of Plexiform Neurofibroma Results in Tumor Shrinkage"],"prefix":"10.1016","volume":"385","author":[{"given":"Mark","family":"Jackson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niousha","family":"Ahmari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4239-5659","authenticated-orcid":false,"given":"Jianqiang","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tilat A.","family":"Rizvi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Fugate","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mi-OK","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Dombi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heribert","family":"Arnhof","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guido","family":"Boehmelt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias J.","family":"D\u00fcchs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clive J.","family":"Long","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Udo","family":"Maier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Trapani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco H.","family":"Hofmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy","family":"Ratner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1124\/jpet.122.001431_bib1","doi-asserted-by":"crossref","DOI":"10.1016\/j.bbcan.2020.188445","article-title":"SOS GEFs in health and disease","volume":"1874","author":"Baltan\u00e1s","year":"2020","journal-title":"Biochim Biophys Acta Rev Cancer"},{"key":"10.1124\/jpet.122.001431_bib2","doi-asserted-by":"crossref","first-page":"4900","DOI":"10.4049\/jimmunol.1500579","article-title":"Sos1 regulates macrophage podosome assembly and macrophage invasive capacity","volume":"195","author":"Baruzzi","year":"2015","journal-title":"J Immunol"},{"key":"10.1124\/jpet.122.001431_bib3","doi-asserted-by":"crossref","first-page":"7143","DOI":"10.1038\/s41598-017-07101-2","article-title":"Characterisation of lung macrophage subpopulations in COPD patients and controls","volume":"7","author":"Dewhurst","year":"2017","journal-title":"Sci Rep"},{"key":"10.1124\/jpet.122.001431_bib4","doi-asserted-by":"crossref","first-page":"2550","DOI":"10.1056\/NEJMoa1605943","article-title":"Activity of selumetinib in neurofibromatosis type 1-related plexiform neurofibromas","volume":"375","author":"Dombi","year":"2016","journal-title":"N Engl J Med"},{"key":"10.1124\/jpet.122.001431_bib5","doi-asserted-by":"crossref","DOI":"10.1084\/jem.20191847","article-title":"Macrophage morphology correlates with single-cell diversity and prognosis in colorectal liver metastasis","volume":"217","author":"Donadon","year":"2020","journal-title":"J Exp Med"},{"key":"10.1124\/jpet.122.001431_bib6","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1038\/s41591-020-01193-6","article-title":"Cabozantinib for neurofibromatosis type 1-related plexiform neurofibromas: a phase 2 trial","volume":"27","author":"Fisher","year":"2021","journal-title":"Nat Med"},{"key":"10.1124\/jpet.122.001431_bib7","doi-asserted-by":"crossref","first-page":"2876","DOI":"10.1038\/s41388-018-0600-x","article-title":"STAT3 inhibition reduces macrophage number and tumor growth in neurofibroma","volume":"38","author":"Fletcher","year":"2019","journal-title":"Oncogene"},{"key":"10.1124\/jpet.122.001431_bib8","doi-asserted-by":"crossref","first-page":"1430","DOI":"10.1056\/NEJMoa1912735","article-title":"Selumetinib in children with inoperable plexiform neurofibromas","volume":"382","author":"Gross","year":"2020","journal-title":"N Engl J Med"},{"key":"10.1124\/jpet.122.001431_bib9","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1515\/hsz-2014-0257","article-title":"Ras activation revisited: role of GEF and GAP systems","volume":"396","author":"Hennig","year":"2015","journal-title":"Biol Chem"},{"key":"10.1124\/jpet.122.001431_bib10","doi-asserted-by":"crossref","first-page":"2551","DOI":"10.1073\/pnas.1812963116","article-title":"Discovery of potent SOS1 inhibitors that block RAS activation via disruption of the RAS-SOS1 interaction","volume":"116","author":"Hillig","year":"2019","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1124\/jpet.122.001431_bib11","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1158\/2159-8290.CD-20-0142","article-title":"BI-3406, a potent and selective SOS1-KRAS interaction inhibitor, is effective in KRAS-driven cancers through combined MEK inhibition","volume":"11","author":"Hofmann","year":"2021","journal-title":"Cancer Discov"},{"key":"10.1124\/jpet.122.001431_bib12","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1172\/JCI60578","article-title":"MEK inhibition exhibits efficacy in human and mouse neurofibromatosis tumors","volume":"123","author":"Jessen","year":"2013","journal-title":"J Clin Invest"},{"key":"10.1124\/jpet.122.001431_bib13","doi-asserted-by":"crossref","first-page":"1709","DOI":"10.1002\/pbc.25546","article-title":"Preclinical assessments of the MEK inhibitor PD-0325901 in a mouse model of neurofibromatosis type 1","volume":"62","author":"Jousma","year":"2015","journal-title":"Pediatr Blood Cancer"},{"key":"10.1124\/jpet.122.001431_bib13a","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.cbpa.2021.02.014","article-title":"Targeting Son of Sevenless 1: the pacemaker of KRAS","volume":"62","author":"Kessler","year":"2021","journal-title":"Curr Opin Chem Biol"},{"key":"10.1124\/jpet.122.001431_bib14","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1002\/(SICI)1098-2264(199903)24:3<283::AID-GCC15>3.0.CO;2-K","article-title":"Loss of NF1 allele in Schwann cells but not in fibroblasts derived from an NF1-associated neurofibroma","volume":"24","author":"Kluwe","year":"1999","journal-title":"Genes Chromosomes Cancer"},{"key":"10.1124\/jpet.122.001431_bib15","doi-asserted-by":"crossref","DOI":"10.1016\/j.ctrv.2020.102137","article-title":"MEK inhibitor resistance mechanisms and recent developments in combination trials","volume":"92","author":"Kun","year":"2021","journal-title":"Cancer Treat Rev"},{"key":"10.1124\/jpet.122.001431_bib16","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1038\/s41580-020-0255-7","article-title":"ERK signalling: a master regulator of cell behaviour, life and fate","volume":"21","author":"Lavoie","year":"2020","journal-title":"Nat Rev Mol Cell Biol"},{"key":"10.1124\/jpet.122.001431_bib18a","doi-asserted-by":"crossref","first-page":"2848","DOI":"10.1172\/JCI99424","article-title":"Contributions of inflammation and tumor microenvironment to neurofibroma tumorigenesis","volume":"128","author":"Liao","year":"2018","journal-title":"J Clin Invest"},{"key":"10.1124\/jpet.122.001431_bib18","doi-asserted-by":"crossref","first-page":"17253","DOI":"10.1073\/pnas.1308887110","article-title":"Modulation of macrophage phenotype by cell shape","volume":"110","author":"McWhorter","year":"2013","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1124\/jpet.122.001431_bib19","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.humpath.2017.05.010","article-title":"Histopathologic evaluation of atypical neurofibromatous tumors and their transformation into malignant peripheral nerve sheath tumor in patients with neurofibromatosis 1-a consensus overview","volume":"67","author":"Miettinen","year":"2017","journal-title":"Hum Pathol"},{"key":"10.1124\/jpet.122.001431_bib20","doi-asserted-by":"crossref","first-page":"20020","DOI":"10.1074\/jbc.M000981200","article-title":"Regulatory proteins of R-Ras, TC21\/R-Ras2, and M-Ras\/R-Ras3","volume":"275","author":"Ohba","year":"2000","journal-title":"J Biol Chem"},{"key":"10.1124\/jpet.122.001431_bib21","doi-asserted-by":"crossref","first-page":"3168","DOI":"10.1038\/onc.2016.464","article-title":"The primacy of NF1 loss as the driver of tumorigenesis in neurofibromatosis type 1-associated plexiform neurofibromas","volume":"36","author":"Pemov","year":"2017","journal-title":"Oncogene"},{"key":"10.1124\/jpet.122.001431_bib22","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0035711","article-title":"Quantitative assessment of whole-body tumor burden in adult patients with neurofibromatosis","volume":"7","author":"Plotkin","year":"2012","journal-title":"PLoS One"},{"key":"10.1124\/jpet.122.001431_bib23","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1007\/s00401-012-1056-7","article-title":"Neurofibroma-associated macrophages play roles in tumor growth and response to pharmacological inhibition","volume":"125","author":"Prada","year":"2013","journal-title":"Acta Neuropathol"},{"key":"10.1124\/jpet.122.001431_bib24","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1093\/oxfordjournals.aje.a010118","article-title":"NF1 gene and neurofibromatosis 1","volume":"151","author":"Rasmussen","year":"2000","journal-title":"Am J Epidemiol"},{"key":"10.1124\/jpet.122.001431_bib25","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1038\/nrc3911","article-title":"A RASopathy gene commonly mutated in cancer: the neurofibromatosis type 1 tumour suppressor","volume":"15","author":"Ratner","year":"2015","journal-title":"Nat Rev Cancer"},{"key":"10.1124\/jpet.122.001431_bib35","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/S0076-6879(05)07003-5","article-title":"Schwann cell preparation from single mouse embryos: analyses of neurofibromin function in Schwann cells","volume":"407","author":"Ratner","year":"2006","journal-title":"Methods Enzymol"},{"key":"10.1124\/jpet.122.001431_bib26","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1038\/s41551-018-0236-8","article-title":"TLR7\/8-agonist-loaded nanoparticles promote the polarization of tumour-associated macrophages to enhance cancer immunotherapy","volume":"2","author":"Rodell","year":"2018","journal-title":"Nat Biomed Eng"},{"key":"10.1124\/jpet.122.001431_bib27","doi-asserted-by":"crossref","DOI":"10.1101\/cshperspect.a031500","article-title":") Ras-specific GTPase-activating proteins-structures, mechanisms, and interactions","volume":"9","author":"Scheffzek","year":"2019","journal-title":"Cold Spring Harb Perspect Med"},{"key":"10.1124\/jpet.122.001431_bib28","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1038\/90148","article-title":"Mitotic recombination effects homozygosity for NF1 germline mutations in neurofibromas","volume":"28","author":"Serra","year":"2001","journal-title":"Nat Genet"},{"key":"10.1124\/jpet.122.001431_bib29","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1146\/annurev-pathol-011811-132441","article-title":"Pathogenesis of plexiform neurofibroma: tumor-stromal\/hematopoietic interactions in tumor progression","volume":"7","author":"Staser","year":"2012","journal-title":"Annu Rev Pathol"},{"key":"10.1124\/jpet.122.001431_bib31","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1038\/jid.2014.465","article-title":"Incidence and mortality of neurofibromatosis: a total population study in Finland","volume":"135","author":"Uusitalo","year":"2015","journal-title":"J Invest Dermatol"},{"key":"10.1124\/jpet.122.001431_bib32","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1200\/JCO.20.02220","article-title":"NF106: a Neurofibromatosis Clinical Trials Consortium phase II trial of the MEK inhibitor mirdametinib (PD-0325901) in adolescents and adults with NF1-related plexiform neurofibromas","volume":"39","author":"Weiss","year":"2021","journal-title":"J Clin Oncol"},{"key":"10.1124\/jpet.122.001431_bib33","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1093\/neuonc\/nou004","article-title":"Phase 2 randomized, flexible crossover, double-blinded, placebo-controlled trial of the farnesyltransferase inhibitor tipifarnib in children and young adults with neurofibromatosis type 1 and progressive plexiform neurofibromas","volume":"16","author":"Widemann","year":"2014","journal-title":"Neuro-oncol"},{"key":"10.1124\/jpet.122.001431_bib36","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1002\/pbc.23015","article-title":"Preclincial testing of sorafenib and RAD001 in the Nf(flox\/flox); DhhCre mouse model of plexiform neurofibroma using magnetic resonance imaging","volume":"58","author":"Wu","year":"2012","journal-title":"Pediatr Blood Cancer"},{"key":"10.1124\/jpet.122.001431_bib34","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.ccr.2007.12.027","article-title":"Plexiform and dermal neurofibromas and pigmentation are caused by Nf1 loss in desert hedgehog-expressing cells","volume":"13","author":"Wu","year":"2008","journal-title":"Cancer Cell"},{"key":"10.1124\/jpet.122.001431_bib37","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/s41593-020-0618-6","article-title":"Profiling peripheral nerve macrophages reveals two macrophage subsets with distinct localization, transcriptome and response to injury","volume":"23","author":"Ydens","year":"2020","journal-title":"Nat Neurosci"}],"container-title":["The Journal of Pharmacology and Experimental Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S002235652400435X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S002235652400435X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1124\/jpet.122.001431","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T13:28:45Z","timestamp":1739971725000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S002235652400435X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5]]},"references-count":37,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2023,5]]}},"alternative-id":["S002235652400435X"],"URL":"https:\/\/doi.org\/10.1124\/jpet.122.001431","relation":{},"ISSN":["0022-3565"],"issn-type":[{"value":"0022-3565","type":"print"}],"subject":[],"published":{"date-parts":[[2023,5]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Combining SOS1 and MEK Inhibitors in a Murine Model of Plexiform Neurofibroma Results in Tumor Shrinkage","name":"articletitle","label":"Article Title"},{"value":"The Journal of Pharmacology and Experimental Therapeutics","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1124\/jpet.122.001431","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"U.S. Government work not protected by U.S. copyright.","name":"copyright","label":"Copyright"}]}}