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dc.contributor.authorSanclemente, Manuel 
dc.contributor.authorFrancoz, Sarah
dc.contributor.authorEsteban-Burgos, Laura 
dc.contributor.authorBousquet-Mur, Emilie
dc.contributor.authorDjurec, Magdolna
dc.contributor.authorLopez-Casas, Pedro P
dc.contributor.authorHidalgo, Manuel 
dc.contributor.authorGuerra, Carmen 
dc.contributor.authorDrosten, Matthias 
dc.contributor.authorMusteanu, Mónica 
dc.contributor.authorBarbacid, Mariano 
dc.date.accessioned2019-08-21T10:06:42Z
dc.date.available2019-08-21T10:06:42Z
dc.date.issued2018-05-01
dc.identifier.citationCancer Cell. 2018;33(2):217-228.es_ES
dc.identifier.issn15356108es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/8311
dc.description.abstractA quarter of all solid tumors harbor KRAS oncogenes. Yet, no selective drugs have been approved to treat these malignancies. Genetic interrogation of the MAPK pathway revealed that systemic ablation of MEK or ERK kinases in adult mice prevent tumor development but are unacceptably toxic. Here, we demonstrate that ablation of c-RAF expression in advanced tumors driven by KrasG12V/Trp53 mutations leads to significant tumor regression with no detectable appearance of resistance mechanisms. Tumor regression results from massive apoptosis. Importantly, systemic abrogation of c-RAF expression does not inhibit canonical MAPK signaling, hence, resulting in limited toxicities. These results are of significant relevance for the design of therapeutic strategies to treat K-RAS mutant cancers.es_ES
dc.description.sponsorshipWe thank David Kirsch for providing theTrp53F/Fstrain. We thank Dr. ManuelMorente for his advice in histopathological analysis. We also thank M. SanRoman, C. Lechuga, R. Villar, P. Villanueva, N. Cabrera, J. Condo, M. Munoz,and R. Blasco for excellent technical support. This work was supported bygrants from the European Research Council (ERC-2009-AdG/250297-RASAHEAD and ERC-2015-AdG/695566,THERACAN), EU-Framework Program(HEALTH-F2-2010-259770/LUNGTARGET and HEALTH-2010-260791/EUROCANPLATFORM), Spanish Ministry of Economy and Competitiveness(SAF2011-30173 and SAF2014-59864-R) and Autonomous Community ofMadrid (S2011/BDM-2470/ONCOCYCLE) to M.B. M.B. is a recipient of anEndowed Chair from the AXA Research Fund. M.S. is the recipient of anFPU fellowship from the Spanish Ministry of Education. S.F. was supportedby a FEBS Long-Term Fellowship and a Sara Borrell grant from the Institutode Salud Carlos III. L.E.-B. is the recipient of an FPI fellowship from the Span-ish Ministry of Economy and Competitiveness.es_ES
dc.language.isoenges_ES
dc.publisherCell Press es_ES
dc.type.hasVersionAMes_ES
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subjectKras oncogenees_ES
dc.subjectMAPK signalinges_ES
dc.subjectc-RAFes_ES
dc.subjectlung canceres_ES
dc.subjectmouse models of canceres_ES
dc.subjecttherapy strategyes_ES
dc.subjecttoxicityes_ES
dc.subject.meshAdenocarcinoma of Lung es_ES
dc.subject.meshAnimals es_ES
dc.subject.meshCell Line, Tumor es_ES
dc.subject.meshGenes, ras es_ES
dc.subject.meshMice es_ES
dc.subject.meshMitogen-Activated Protein Kinase Kinases es_ES
dc.subject.meshMutation es_ES
dc.subject.meshProtein Kinase Inhibitors es_ES
dc.subject.meshProto-Oncogene Proteins es_ES
dc.subject.meshProto-Oncogene Proteins B-raf es_ES
dc.subject.meshProto-Oncogene Proteins c-raf es_ES
dc.subject.meshras Proteins es_ES
dc.titlec-RAF Ablation Induces Regression of Advanced Kras/Trp53 Mutant Lung Adenocarcinomas by a Mechanism Independent of MAPK Signalinges_ES
dc.typejournal articlees_ES
dc.rights.licenseAtribución-NoComercial-CompartirIgual 4.0 Internacional*
dc.identifier.pubmedID29395869es_ES
dc.format.volume33es_ES
dc.format.number2es_ES
dc.format.page217-228.e4es_ES
dc.identifier.doi10.1016/j.ccell.2017.12.014es_ES
dc.contributor.funderUnión Europea. Comisión Europea. European Research Council (ERC) 
dc.contributor.funderMinisterio de Economía e Innovación (España) 
dc.contributor.funderComunidad de Madrid (España) 
dc.contributor.funderFundación AXA 
dc.identifier.e-issn1878-3686es_ES
dc.relation.publisherversionhttps://doi.org/10.1016/j.ccell.2017.12.014es_ES
dc.identifier.journalCancer celles_ES
dc.repisalud.institucionCNIOes_ES
dc.repisalud.orgCNIOCNIO::Grupos de investigación::Grupo de Oncología Experimentales_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/EC/FP7/250297es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/EC/H2020/695566es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/SAF2011-30173es_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/SAF2014-59864-Res_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/S2011/BDM-2470/ONCOCYCLEes_ES
dc.rights.accessRightsopen accesses_ES


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