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dc.contributor.author | Sanclemente, Manuel | |
dc.contributor.author | Francoz, Sarah | |
dc.contributor.author | Esteban-Burgos, Laura | |
dc.contributor.author | Bousquet-Mur, Emilie | |
dc.contributor.author | Djurec, Magdolna | |
dc.contributor.author | Lopez-Casas, Pedro P | |
dc.contributor.author | Hidalgo, Manuel | |
dc.contributor.author | Guerra, Carmen | |
dc.contributor.author | Drosten, Matthias | |
dc.contributor.author | Musteanu, Mónica | |
dc.contributor.author | Barbacid, Mariano | |
dc.date.accessioned | 2019-08-21T10:06:42Z | |
dc.date.available | 2019-08-21T10:06:42Z | |
dc.date.issued | 2018-05-01 | |
dc.identifier.citation | Cancer Cell. 2018;33(2):217-228. | es_ES |
dc.identifier.issn | 15356108 | es_ES |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/8311 | |
dc.description.abstract | A 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.sponsorship | We 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.iso | eng | es_ES |
dc.publisher | Cell Press | es_ES |
dc.type.hasVersion | AM | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-sa/4.0/ | * |
dc.subject | Kras oncogene | es_ES |
dc.subject | MAPK signaling | es_ES |
dc.subject | c-RAF | es_ES |
dc.subject | lung cancer | es_ES |
dc.subject | mouse models of cancer | es_ES |
dc.subject | therapy strategy | es_ES |
dc.subject | toxicity | es_ES |
dc.subject.mesh | Adenocarcinoma of Lung | es_ES |
dc.subject.mesh | Animals | es_ES |
dc.subject.mesh | Cell Line, Tumor | es_ES |
dc.subject.mesh | Genes, ras | es_ES |
dc.subject.mesh | Mice | es_ES |
dc.subject.mesh | Mitogen-Activated Protein Kinase Kinases | es_ES |
dc.subject.mesh | Mutation | es_ES |
dc.subject.mesh | Protein Kinase Inhibitors | es_ES |
dc.subject.mesh | Proto-Oncogene Proteins | es_ES |
dc.subject.mesh | Proto-Oncogene Proteins B-raf | es_ES |
dc.subject.mesh | Proto-Oncogene Proteins c-raf | es_ES |
dc.subject.mesh | ras Proteins | es_ES |
dc.title | c-RAF Ablation Induces Regression of Advanced Kras/Trp53 Mutant Lung Adenocarcinomas by a Mechanism Independent of MAPK Signaling | es_ES |
dc.type | journal article | es_ES |
dc.rights.license | Atribución-NoComercial-CompartirIgual 4.0 Internacional | * |
dc.identifier.pubmedID | 29395869 | es_ES |
dc.format.volume | 33 | es_ES |
dc.format.number | 2 | es_ES |
dc.format.page | 217-228.e4 | es_ES |
dc.identifier.doi | 10.1016/j.ccell.2017.12.014 | es_ES |
dc.contributor.funder | Unión Europea. Comisión Europea. European Research Council (ERC) | |
dc.contributor.funder | Ministerio de Economía e Innovación (España) | |
dc.contributor.funder | Comunidad de Madrid (España) | |
dc.contributor.funder | Fundación AXA | |
dc.identifier.e-issn | 1878-3686 | es_ES |
dc.relation.publisherversion | https://doi.org/10.1016/j.ccell.2017.12.014 | es_ES |
dc.identifier.journal | Cancer cell | es_ES |
dc.repisalud.institucion | CNIO | es_ES |
dc.repisalud.orgCNIO | CNIO::Grupos de investigación::Grupo de Oncología Experimental | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/EC/FP7/250297 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/EC/H2020/695566 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/SAF2011-30173 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/SAF2014-59864-R | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/ES/S2011/BDM-2470/ONCOCYCLE | es_ES |
dc.rights.accessRights | open access | es_ES |