dc.creator | Quintanal Villalonga, Álvaro Diego | es |
dc.creator | Molina Pinelo, Sonia | es |
dc.creator | Cirauqui, Cristina | es |
dc.creator | Ojeda Márquez, Laura | es |
dc.creator | Marrugal, Ángela | es |
dc.creator | Suárez, Rocío | es |
dc.creator | Conde, Esther | es |
dc.creator | Ponce Aix, Santiago | es |
dc.creator | Enguita, Ana Belén | es |
dc.creator | Ferrer, Irene | es |
dc.creator | Paz Ares, Luis | es |
dc.creator | Carnero Moya, Amancio | es |
dc.date.accessioned | 2019-05-31T09:17:31Z | |
dc.date.available | 2019-05-31T09:17:31Z | |
dc.date.issued | 2019-04 | |
dc.identifier.citation | 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. | |
dc.identifier.issn | 1556-0864 | es |
dc.identifier.uri | https://hdl.handle.net/11441/87075 | |
dc.description.abstract | 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. | es |
dc.description.sponsorship | ISCIII PI14/01964 PIE15/00076 PI17/00778 DTS17/00089 PI15/00045 PI17/00033 PI16/01311 FI12/00429 | es |
dc.description.sponsorship | CIBERONC CD16/12/00442 | es |
dc.description.sponsorship | FEDER CD16/12/00442 PI16/01311 | es |
dc.description.sponsorship | Spanish Ministry of Economy and Competitiveness PI15/00045 | es |
dc.description.sponsorship | Ministry of Health and Social Welfare of Junta de Andalucía PI-0046-2012 C-0040-2016 | es |
dc.description.sponsorship | Ministry of Equality, Health and Social Policies of the Junta de Andalucía PI- 0029-2013 | es |
dc.description.sponsorship | Comunidad de Madrid B2017/BMD3884 | es |
dc.description.sponsorship | Ministry of Education, Culture and Sports FPU13/02595 | es |
dc.format | application/pdf | es |
dc.language.iso | eng | es |
dc.publisher | Elsevier | es |
dc.relation.ispartof | Journal of Thoracic Oncology, 14 (4), 641-655. | |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.subject | FGFR1 | es |
dc.subject | EGFR | es |
dc.subject | Cooperation | es |
dc.subject | Combined inhibition | es |
dc.title | FGFR1 Cooperates with EGFR in Lung Cancer Oncogenesis, and Their Combined Inhibition Shows Improved Efficacy | es |
dc.type | info:eu-repo/semantics/article | es |
dcterms.identifier | https://ror.org/03yxnpp24 | |
dc.type.version | info:eu-repo/semantics/publishedVersion | es |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | es |
dc.contributor.affiliation | Instituto de Biomedicina de Sevilla (IBIS) | es |
dc.relation.projectID | PI14/01964 | es |
dc.relation.projectID | PIE15/00076 | es |
dc.relation.projectID | PI17/00778 | es |
dc.relation.projectID | DTS17/00089 | es |
dc.relation.projectID | CD16/12/00442 | es |
dc.relation.projectID | PI15/00045 | es |
dc.relation.projectID | PI-0046-2012 | es |
dc.relation.projectID | C-0040-2016 | es |
dc.relation.projectID | PI17/00033 | es |
dc.relation.projectID | AIO2015 | es |
dc.relation.projectID | PI-0029-2013 | es |
dc.relation.projectID | B2017/BMD388 | es |
dc.relation.projectID | PI16/01311 | es |
dc.relation.projectID | FI12/00429 | es |
dc.relation.projectID | FPU13/02595 | es |
dc.relation.publisherversion | http://dx.doi.org/10.1016/j.jtho.2018.12.021 | es |
dc.identifier.doi | 10.1016/j.jtho.2018.12.021 | es |
idus.format.extent | 15 p. | es |
dc.journaltitle | Journal of Thoracic Oncology | es |
dc.publication.volumen | 14 | es |
dc.publication.issue | 4 | es |
dc.publication.initialPage | 641 | es |
dc.publication.endPage | 655 | es |