RT Journal Article T1 FGFR1 and FGFR4 oncogenicity depends on n-cadherin and their co-expression may predict FGFR-targeted therapy efficacy A1 Quintanal-Villalonga, Álvaro A1 Ferrer, Irene A1 Guruceaga, Elizabeth A1 Cirauqui, Cristina A1 Marrugal, Ángela A1 Ojeda, Laura A1 García, Santiago A1 Zugazagoitia, Jon A1 Muñoz-Galván, Sandra A1 Lopez-Rios, Fernando A1 Montuenga, Luis A1 Vicent, Silvestre A1 Molina-Pinelo, Sonia A1 Carnero, Amancio A1 Paz-Ares, Luis K1 FGFR1 K1 FGFR4 K1 N-cadherin K1 Predictive biomarker K1 FGFR inhibitors K1 Fibroblast growth factor receptor 1 K1 Fibroblast growth factor receptor 4 K1 Biomarkers K1 Lung neoplasms K1 Cadherinas K1 Receptor tipo 1 de factor de crecimiento de fibroblastos K1 Receptor tipo 4 de factor de crecimiento de fibroblastos K1 Biomarcadores K1 Neoplasias pulmonares AB Background: 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. PB Elsevier YR 2020 FD 2020-02-27 LK http://hdl.handle.net/10668/4460 UL http://hdl.handle.net/10668/4460 LA en NO Quintanal-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;53:102683 DS RISalud RD Apr 18, 2025