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 Ojeda Márquez, Laura
A1 López-Ríos Moreno, Fernando
A1 Paz-Ares Rodríguez, Luis Gonzaga
AB BackgroundFibroblast 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.MethodsIn 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.FindingsWe 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.InterpretationOur 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
SN 32114392
SN 2352-3964
YR 2020
FD 2020-02-27
LK https://hdl.handle.net/20.500.14352/118240
UL https://hdl.handle.net/20.500.14352/118240
LA eng
NO Quintanal-Villalonga Á, Ferrer I, Guruceaga E, Cirauqui C, Marrugal Á, Ojeda L, García S, Zugazagoitia J, Muñoz-Galván S, Lopez-Rios F, Montuenga L, Vicent S, Molina-Pinelo S, Carnero A, Paz-Ares L. FGFR1 and FGFR4 oncogenicity depends on n-cadherin and their co-expression may predict FGFR-targeted therapy efficacy. EBioMedicine. 2020 Mar;53:102683. doi: 10.1016/j.ebiom.2020.102683.
NO Fondos FEDER
NO European Commission
NO Ministerio de Economía y Competitividad (España)
NO Instituto de Salud Carlos III (España)
NO Comunidad Autónoma de Madrid
NO Junta de Andalucía
NO Mutua Madrileña
NO Ministerio de Educación, Cultura y Deportes (España)
NO Asociación Española Contra el Cáncer
DS Docta Complutense
RD 18 abr 2025