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dc.contributor.authorQuintanal-Villalonga, Alvaro 
dc.contributor.authorFerrer, Irene
dc.contributor.authorGuruceaga, Elizabeth
dc.contributor.authorCirauqui, Cristina
dc.contributor.authorMarrugal, Ángela
dc.contributor.authorOjeda, Laura
dc.contributor.authorGarcía, Santiago
dc.contributor.authorZugazagoitia, Jon
dc.contributor.authorMuñoz-Galván, Sandra
dc.contributor.authorLopez-Rios, Fernando
dc.contributor.authorMontuenga, Luis
dc.contributor.authorVicent, Silvestre
dc.contributor.authorMolina-Pinelo, Sonia
dc.contributor.authorCarnero, Amancio
dc.contributor.authorPaz Ares, Luis Gonzaga
dc.description.abstractFibroblast growth factor receptor (FGFR)1 and FGFR4 have been associated with tumorigenesis in a variety of tumour types. As a therapeutic approach, their inhibition has been attempted in different types of malignancies, including lung cancer, and was initially focused on FGFR1-amplified tumours, though with limited success. In vitro and in vivo functional assessments of the oncogenic potential of downregulated/overexpressed genes in isogenic cell lines were performed, as well as inhibitor efficacy tests in vitro and in vivo in patient-derived xenografts (PDXs). mRNA was extracted from FFPE non-small cell lung cancer samples to determine the prognostic potential of the genes under study. We provide in vitro and in vivo evidence showing that expression of the adhesion molecule N-cadherin is key for the oncogenic role of FGFR1/4 in non-small cell lung cancer. According to this, assessment of the expression of genes in different lung cancer patient cohorts showed that FGFR1 or FGFR4 expression alone showed no prognostic potential, and that only co-expression of FGFR1 and/or FGFR4 with N-cadherin inferred a poorer outcome. Treatment of high-FGFR1 and/or FGFR4-expressing lung cancer cell lines and patient-derived xenografts with selective FGFR inhibitors showed high efficacy, but only in models with high FGFR1/4 and N-cadherin expression. Our data show that the determination of the expression of FGFR1 or FGFR4 alone is not sufficient to predict anti-FGFR therapy efficacy; complementary determination of N-cadherin expression may further optimise patient selection for this therapeutic strategy.es_ES
dc.description.sponsorshipThis work was funded by the Community of Madrid, the ISCIII co-funded by FEDER from Regional Development European Funds (European Union), the Spanish Ministry of Economy and Competitiveness, the Mutua Madrilena Foundation, the Ministry of Health and Social Welfare of Junta de Andalucia, the AECC scientific foundation and the Spanish Ministry of Education, Culture and Sport.es_ES
dc.publisherElsevier es_ES
dc.subjectPredictive biomarkeres_ES
dc.subjectFGFR inhibitorses_ES
dc.titleFGFR1 and FGFR4 oncogenicity depends on n-cadherin and their co-expression may predict FGFR-targeted therapy efficacy.es_ES
dc.typejournal articlees_ES
dc.rights.licenseAtribución-NoComercial-CompartirIgual 4.0 Internacional*
dc.contributor.funderComunidad de Madrid 
dc.contributor.funderEuropean Regional Development Fund 
dc.contributor.funderFundación Mutua Madrileña 
dc.contributor.funderMinisterio de Economía y Competitividad (España) 
dc.contributor.funderRegional Government of Andalusia (España) 
dc.contributor.funderAsociación Española Contra el Cáncer 
dc.relation.publisherversion 10.1016/j.ebiom.2020.102683.es_ES
dc.repisalud.orgCNIOCNIO::Unidades técnicas::Unidad de Investigación Clínica de Cáncer Pulmón H12O-CNIOes_ES
dc.rights.accessRightsopen accesses_ES

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Atribución-NoComercial-CompartirIgual 4.0 Internacional
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