2024-03-28T20:44:12Zhttp://repisalud.isciii.es/oai/requestoai:repisalud.isciii.es:20.500.12105/109892022-09-20T07:22:59Zcom_20.500.12105_2174com_20.500.12105_2051com_20.500.12105_2173col_20.500.12105_2175
00925njm 22002777a 4500
dc
Quintanal-Villalonga, Alvaro
author
Ferrer, Irene
author
Guruceaga, Elizabeth
author
Cirauqui, Cristina
author
Marrugal, Ángela
author
Ojeda, Laura
author
García, Santiago
author
Zugazagoitia, Jon
author
Muñoz-Galván, Sandra
author
Lopez-Rios, Fernando
author
Montuenga, Luis
author
Vicent, Silvestre
author
Molina-Pinelo, Sonia
author
Carnero, Amancio
author
Paz Ares, Luis Gonzaga
author
2020-03
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.
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.
EBioMedicine.2020;53:102683
http://hdl.handle.net/20.500.12105/10989
32114392
10.1016/j.ebiom.2020.102683
2352-3964
EBioMedicine
FGFR1
FGFR4
N-cadherin
Predictive biomarker
FGFR inhibitors
FGFR1 and FGFR4 oncogenicity depends on n-cadherin and their co-expression may predict FGFR-targeted therapy efficacy.