Quintanal-Villalonga, ÁlvaroFerrer, IreneGuruceaga, ElizabethCirauqui, CristinaMarrugal, ÁngelaOjeda, LauraGarcía, SantiagoZugazagoitia, JonMuñoz-Galván, SandraLopez-Rios, FernandoMontuenga, LuisVicent, SilvestreMolina-Pinelo, SoniaCarnero, AmancioPaz-Ares, Luis2022-12-052022-12-052020-02-27Quintanal-Villalonga Á, Ferrer I, Guruceaga E, Cirauqui C, Marrugal Á, Ojeda L, et al. FGFR1 and FGFR4 oncogenicity depends on n-cadherin and their co-expression may predict FGFR-targeted therapy efficacy. EBioMedicine. 2020 Mar;53:102683http://hdl.handle.net/10668/4460Background: Fibroblast 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. Methods: 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. Findings: 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. Interpretation: 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.enAttribution-NonCommercial-NoDerivatives 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-nd/4.0/FGFR1FGFR4N-cadherinPredictive biomarkerFGFR inhibitorsFibroblast growth factor receptor 1Fibroblast growth factor receptor 4BiomarkersLung neoplasmsCadherinasReceptor tipo 1 de factor de crecimiento de fibroblastosReceptor tipo 4 de factor de crecimiento de fibroblastosBiomarcadoresNeoplasias pulmonaresMedical Subject Headings::Organisms::Eukaryota::AnimalsMedical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antineoplastic AgentsMedical Subject Headings::Chemicals and Drugs::Organic Chemicals::Amides::BenzamidesMedical Subject Headings::Chemicals and Drugs::Biological Factors::Biological MarkersMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Glycoproteins::Membrane Glycoproteins::Cell Adhesion Molecules::CadherinsMedical Subject Headings::Diseases::Neoplasms::Neoplasms by Site::Thoracic Neoplasms::Respiratory Tract Neoplasms::Lung Neoplasms::Bronchial Neoplasms::Carcinoma, Bronchogenic::Carcinoma, Non-Small-Cell LungMedical Subject Headings::Anatomy::Cells::Cells, Cultured::Cell Line::Cell Line, TumorMedical Subject Headings::Check Tags::FemaleMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Diseases::Neoplasms::Neoplasms by Site::Thoracic Neoplasms::Respiratory Tract Neoplasms::Lung NeoplasmsMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::MiceMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice::Mice, Mutant Strains::Mice, NudeMedical Subject Headings::Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds, 1-Ring::PiperazinesMedical Subject Headings::Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds, 1-Ring::Azoles::PyrazolesMedical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Transferases::Phosphotransferases::Phosphotransferases (Alcohol Group Acceptor)::Protein Kinases::Protein-Tyrosine Kinases::Receptor Protein-Tyrosine Kinases::Receptor, Fibroblast Growth Factor, Type 1Medical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Transferases::Phosphotransferases::Phosphotransferases (Alcohol Group Acceptor)::Protein Kinases::Protein-Tyrosine Kinases::Receptor Protein-Tyrosine Kinases::Receptor, Fibroblast Growth Factor, Type 4Medical Subject Headings::Anatomy::Cells::Cells, Cultured::Tumor Cells, CulturedMedical Subject Headings::Phenomena and Processes::Physiological Phenomena::Pharmacological Phenomena::Drug Resistance::Drug Resistance, Neoplasmresearch article32114392open access10.1016/j.ebiom.2020.1026832352-3964PMC7047190