RT Journal Article
T1 FGFR1 Cooperates with EGFR in Lung Cancer Oncogenesis, and Their Combined Inhibition Shows Improved Efficacy
A1 Quintanal Villalonga, Álvaro
A1 Ponce Aix, Santiago
A1 Enguita Valls, Ana Belén
A1 Paz-Ares Rodríguez, Luis Gonzaga
AB IntroductionThere is substantial evidence for the oncogenic effects of fibroblast growth factor receptor 1 (FGFR1) in many types of cancer, including lung cancer, but the role of this receptor has not been addressed specifically in lung adenocarcinoma.MethodsWe performed FGFR1 and EGFR overexpression and co-overexpression assays in adenocarcinoma and in inmortalized lung cell lines, and we also carried out surrogate and interaction assays. We performed monotherapy and combination EGFR/FGFR inhibitor sensitivity assays in vitro and in vivo in cell line– and patient-derived xenografts. We determined FGFR1 mRNA expression in a cohort of patients with anti–EGFR therapy–treated adenocarcinoma.ResultsWe have reported a cooperative interaction between FGFR1 and EGFR in this context, resulting in increased EGFR activation and oncogenic signaling. We have provided in vitro and in vivo evidence indicating that FGFR1 expression increases tumorigenicity in cells with high EGFR activation in EGFR-mutated and EGFR wild-type models. At the clinical level, we have shown that high FGFR1 expression levels predict higher resistance to erlotinib or gefitinib in a cohort of patients with tyrosine kinase inhibitor–treated EGFR-mutated and EGFR wild-type lung adenocarcinoma. Dual EGFR and FGFR inhibition in FGFR1-overexpressing, EGFR-activated models shows synergistic effects on tumor growth in vitro and in cell line– and patient-derived xenografts, suggesting that patients with tumors bearing these characteristics may benefit from combined EGFR/FGFR inhibition.ConclusionThese results support the extended the use of EGFR inhibitors beyond monotherapy in the EGFR-mutated adenocarcinoma setting in combination with FGFR inhibitors for selected patients with increased FGFR1 overexpression and EGFR activation.
PB Elsevier
YR 2019
FD 2019-01-09
LK https://hdl.handle.net/20.500.14352/116474
UL https://hdl.handle.net/20.500.14352/116474
LA eng
NO Quintanal-Villalonga A, Molina-Pinelo S, Cirauqui C, Ojeda-Márquez L, Marrugal Á, Suarez R, Conde E, Ponce-Aix S, Enguita AB, Carnero A, Ferrer I, Paz-Ares L. FGFR1 Cooperates with EGFR in Lung Cancer Oncogenesis, and Their Combined Inhibition Shows Improved Efficacy. J Thorac Oncol. 2019 Apr;14(4):641-655. doi: 10.1016/j.jtho.2018.12.021. Epub 2019 Jan 9. PMID: 30639621.
DS Docta Complutense
RD 7 abr 2025