Artículo
FGFR1 Cooperates with EGFR in Lung Cancer Oncogenesis, and Their Combined Inhibition Shows Improved Efficacy
Autor/es | Quintanal Villalonga, Álvaro Diego
Molina Pinelo, Sonia Cirauqui, Cristina Ojeda Márquez, Laura Marrugal, Ángela Suárez, Rocío Conde, Esther Ponce Aix, Santiago Enguita, Ana Belén Ferrer, Irene Paz Ares, Luis Carnero Moya, Amancio |
Departamento | Instituto de Biomedicina de Sevilla (IBIS) |
Fecha de publicación | 2019-04 |
Fecha de depósito | 2019-05-31 |
Publicado en |
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Resumen | Introduction:
There is substantial evidence for the onco-
genic effects of
fi
broblast growth factor receptor 1 (FGFR1)
in many types of cancer, including lung cancer, but the role
of this receptor has not been ... Introduction: There is substantial evidence for the onco- genic effects of fi broblast growth factor receptor 1 (FGFR1) in many types of cancer, including lung cancer, but the role of this receptor has not been addressed speci fi cally in lung adenocarcinoma. Methods: We performed FGFR1 and EGFR overexpression and co-overexpression assays in adenocarcinoma and in inmortalized lung cell lines, and we also carried out surrogateandinteractionassays.Weperformedmono- therapy 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 ther- apy – treated adenocarcinoma. Results: We 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 in- creases 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 pre- dict higher resistance to erlotinib or ge fi tinib 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-over expressing, 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 bene fi t from combined EGFR/FGFR inhibition. Conclusion: These results support the extended the use of EGFR inhibitors beyond monotherapy in the EGFR-mutated adenocarcinoma setting in combination with FGFR in- hibitors for selected patients with increased FGFR1 over- expression and EGFR activation. |
Identificador del proyecto | PI14/01964
PIE15/00076 PI17/00778 DTS17/00089 CD16/12/00442 PI15/00045 PI-0046-2012 C-0040-2016 PI17/00033 AIO2015 PI-0029-2013 B2017/BMD388 PI16/01311 FI12/00429 FPU13/02595 |
Cita | Quintanal Villalonga, Á.D., Molina Pinelo, S., Cirauqui, C., Ojeda Márquez, L., Marrugal, Á., Suárez, R.,...,Carnero Moya, A. (2019). FGFR1 Cooperates with EGFR in Lung Cancer Oncogenesis, and Their Combined Inhibition Shows Improved Efficacy. Journal of Thoracic Oncology, 14 (4), 641-655. |
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