Publication:
Complete Regression of Advanced Pancreatic Ductal Adenocarcinomas upon Combined Inhibition of EGFR and C-RAF

Simple item page
dc.contributor.authorBlasco, María Teresa
dc.contributor.authorNavas, Carolina
dc.contributor.authorMartín-Serrano, Guillermo
dc.contributor.authorGraña Castro, Osvaldo
dc.contributor.authorLechuga, Carmen G
dc.contributor.authorMartín-Díaz, Laura
dc.contributor.authorDjurec, Magdolna
dc.contributor.authorLi, Jing
dc.contributor.authorMorales-Cacho, Lucia
dc.contributor.authorEsteban-Burgos, Laura
dc.contributor.authorPerales-Patón, Javier
dc.contributor.authorBousquet-Mur, Emilie
dc.contributor.authorCastellano, Eva
dc.contributor.authorJacob, Harrys K C
dc.contributor.authorCabras, Lavinia
dc.contributor.authorMusteanu, Mónica
dc.contributor.authorDrosten, Matthias
dc.contributor.authorOrtega, Sagrario
dc.contributor.authorMulero, Francisca
dc.contributor.authorSainz, Bruno
dc.contributor.authorDusetti, Nelson
dc.contributor.authorIovanna, Juan
dc.contributor.authorSanchez-Bueno, Francisco
dc.contributor.authorHidalgo, Manuel
dc.contributor.authorKhiabanian, Hossein
dc.contributor.authorRabadan, Raul
dc.contributor.authorAl-Shahrour, Fatima
dc.contributor.authorGuerra, Carmen
dc.contributor.authorBarbacid, Mariano
dc.contributor.funderUnión Europea. Comisión Europea. European Research Council (ERC)
dc.contributor.funderMinisterio de Economía y Competitividad (España)
dc.contributor.funderAsociación Española Contra el Cáncer
dc.contributor.funderLigue Nationale Contre le Cancer (Francia)
dc.contributor.funderNIH - National Cancer Institute (NCI) (Estados Unidos)
dc.contributor.funderFundación La Caixa
dc.contributor.funderFundación AXA
dc.date.accessioned2019-08-21T09:13:18Z
dc.date.available2019-08-21T09:13:18Z
dc.date.issued2019-04-15
dc.descriptionWe thank B. Jime ́nez, M. San Roman, R. Villar, and S. Jime ́nez for excellenttechnical assistance; I. Arago ́n, A. Lo ́pez, F. Dı ́az,and I. Blanco (Animal Facil-ity) for mouse work; G. Visdomine, C. Pen ̃alba, and G. Garaulet (MolecularImaging Unit) for ultrasound studies; P. Vargiu (Transgenic Unit) for help ingenerating theTetO-FlpOstrain; N. Cabrera, A. de Martino (HistopathologyUnit) and M. Morente (Tumor Bank) for histopathological analysis, andC. Blanco and A. Cebria ́(Experimental Therapeutics) for determining theIC50values of gefinitib and erlotinib. Special thanks to J. de la Pen ̃a and E. Ortiz(Servicio de Anatomı ́aPatolo ́gica HCUVA) and T. Escamez and V. Navarro(Biobanco-IMIM) for their help with the PDX tumor models, and to R. Nieto,J.M. Ligo ́s, and M. Montoya (Cytometry Unit, CNIC) for fluorescence-activatedcell sorting analysis of apoptotic cells. This work was supported by grants fromthe European Research Council (advanced grants ERC-AG/250297-RASAHEAD and ERC-AG/695566-THERACAN), from the Spanish Ministry ofEconomy and Competitiveness (SAF2014-59864-R) to M.B. Additional sup-port was also obtained from grants from the Asociacio ́n Espan ̃ola contra elCa ́ncer (GC16173694BARB) to M.B. and B.S., from La Ligue Contre le Cancerto J.I., from the European Research Council (advanced grants ERC-2014-ADG) to M.H., and from the NIH (U54CA193313 and U54CA209997) to R.R.M.T.B was supported by an FPU fellowship from the Spanish Ministry of Edu-cation. C.N. was supported by a Juan de la Cierva Award. M. Djurec waspartially supported by a pre-doctoral fellowship from La Caixa. J.P.-P. wassupported by a Severo Ochoa FPI fellowship from the Spanish Ministry ofEconomy and Competitiveness. M.B. is the recipient of an Endowed Chairfrom the AXA Research Fund.es_ES
dc.description.abstractFive-year survival for pancreatic ductal adenocarcinoma (PDAC) patients remains below 7% due to the lack of effective treatments. Here, we report that combined ablation of EGFR and c-RAF expression results in complete regression of a significant percentage of PDAC tumors driven by Kras/Trp53 mutations in genetically engineered mice. Moreover, systemic elimination of these targets induces toxicities that are well tolerated. Response to this targeted therapy correlates with transcriptional profiles that resemble those observed in human PDACs. Finally, inhibition of EGFR and c-RAF expression effectively blocked tumor progression in nine independent patient-derived xenografts carrying KRAS and TP53 mutations. These results open the door to the development of targeted therapies for PDAC patients.es_ES
dc.description.peerreviewedSíes_ES
dc.format.number4es_ES
dc.format.page573-587.e6es_ES
dc.format.volume35es_ES
dc.identifier.citationCancer Cell. 2019;35(4):573-587.es_ES
dc.identifier.doi10.1016/j.ccell.2019.03.002es_ES
dc.identifier.e-issn1878-3686es_ES
dc.identifier.issn15356108es_ES
dc.identifier.journalCancer celles_ES
dc.identifier.pubmedID30975481es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/8310
dc.language.isoenges_ES
dc.publisherCell Press
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/SAF2014-59864-Res_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/GC16173694BARBes_ES
dc.relation.publisherversionhttps://doi.org/10.1016/j.ccell.2019.03.002es_ES
dc.repisalud.institucionCNIOes_ES
dc.repisalud.orgCNIOCNIO::Grupos de investigación::Grupo de Oncología Experimentales_ES
dc.rights.accessRightsopen accesses_ES
dc.rights.licenseAtribución-NoComercial-CompartirIgual 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subjectCdk4es_ES
dc.subjectEGFRes_ES
dc.subjectErlotinibes_ES
dc.subjectPDX tumor modelses_ES
dc.subjectPancreatic canceres_ES
dc.subjectc-Rafes_ES
dc.subjectTherapeutic mouse modelses_ES
dc.subjectTranscriptional profileses_ES
dc.subjectTumor regressiones_ES
dc.titleComplete Regression of Advanced Pancreatic Ductal Adenocarcinomas upon Combined Inhibition of EGFR and C-RAFes_ES
dc.typejournal articlees_ES
dc.type.hasVersionSMURes_ES
dspace.entity.typePublication
relation.isAuthorOfPublication985e5671-0ac7-4e86-98c2-31a5ffe60751
relation.isAuthorOfPublication92a441f8-dca3-4294-8cd4-03af6bc92faf
relation.isAuthorOfPublication00f5ae15-3f48-4fcd-806e-0ebd27eab767
relation.isAuthorOfPublicationaff72b01-c3b6-455f-b4d5-abd12819cadb
relation.isAuthorOfPublication3064b65c-f19a-4726-a7c1-a4d1664329be
relation.isAuthorOfPublication69c60524-03e3-4bd7-a905-3550ad8f72c9
relation.isAuthorOfPublication142e3ab4-515e-405e-93d5-72ef421c33c4
relation.isAuthorOfPublicationb32f5df7-30c2-4a3e-8f98-e59842b85c61
relation.isAuthorOfPublicatione3ceecfe-c5d7-442a-97d8-087e6883b1b2
relation.isAuthorOfPublication728b1f96-276b-4ab5-8640-8964fb72939f
relation.isAuthorOfPublication.latestForDiscovery985e5671-0ac7-4e86-98c2-31a5ffe60751
relation.isFunderOfPublicationcb2ee04a-8d42-4a64-b3f6-3c156f222b35
relation.isFunderOfPublication77b2fc20-6311-4e46-98a7-83e46257b93b
relation.isFunderOfPublication453a1189-9bca-4be8-8d60-695f50fe028b
relation.isFunderOfPublicationef5576d5-2a85-4ab7-8ca9-d1db9877f7cc
relation.isFunderOfPublicationb589134c-ce3e-4f64-a3f5-83d0a7eb706a
relation.isFunderOfPublicationf04d23ec-a91d-4242-88b0-cc436888f8a2
relation.isFunderOfPublication2333a0bf-1e57-401e-a748-478265970910
relation.isFunderOfPublication.latestForDiscoverycb2ee04a-8d42-4a64-b3f6-3c156f222b35
relation.isPublisherOfPublicationaea619d1-42a6-47f8-84e2-6bc27d6f8300
relation.isPublisherOfPublication.latestForDiscoveryaea619d1-42a6-47f8-84e2-6bc27d6f8300

Files

Original bundle

Now showing 1 - 1 of 1
Thumbnail Image
Name:
CompleteRegressionofAdvancedPancreaticDUCTAL_2019.pdf
Size:
3.04 MB
Format:
Adobe Portable Document Format
Description:
Download

Collections

Grupos de investigación