The pancreatic niche inhibits the effectiveness of sunitinib treatment of pancreatic cancer.

Martínez Bosch, Neus; Enrique Guerrero, Pedro; Moreno, Mireia; José Segarra-Martínez, Anabel; Iglesias García, Mar; Munné-Collado, Jessica; Anta Rodríguez, Héctor, 1988-; Gibert Fernandez, Joan, 1988-; Orozco, Carlos Alberto; Vinaixa Forner, Judith, 1991-; Fillat i Fonts, Cristina; Viñals, Francesc; Navarro Medrano, Pilar

The pancreatic niche inhibits the effectiveness of sunitinib treatment of pancreatic cancer.

Current treatments for pancreatic ductal adenocarcinoma (PDA) are ineffective, making this the 4th leading cause of cancer deaths. Sunitinib is a broad-spectrum inhibitor of tyrosine kinase receptors mostly known for its anti-angiogenic effects. We tested the therapeutic effects of sunitinib in panc...

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Autores:	Martínez Bosch, Neus, Enrique Guerrero, Pedro, Moreno, Mireia, José Segarra-Martínez, Anabel, Iglesias García, Mar, Munné-Collado, Jessica, Anta Rodríguez, Héctor, 1988-, Gibert Fernandez, Joan, 1988-, Orozco, Carlos Alberto, Vinaixa Forner, Judith, 1991-, Fillat i Fonts, Cristina, Viñals, Francesc, Navarro Medrano, Pilar
Tipo de recurso:	artículo
Estado:	Versión publicada
Fecha de publicación:	2016
País:	España
Institución:	Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:	Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:	oai:recercat.cat:10230/27776
Acceso en línea:	http://hdl.handle.net/10230/27776 http://dx.doi.org/10.18632/oncotarget.10199
Access Level:	acceso abierto
Palabra clave:	Pàncrees -- Càncer -- Tractament

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spelling	The pancreatic niche inhibits the effectiveness of sunitinib treatment of pancreatic cancer.Martínez Bosch, NeusEnrique Guerrero, PedroMoreno, MireiaJosé Segarra-Martínez, AnabelIglesias García, MarMunné-Collado, JessicaAnta Rodríguez, Héctor, 1988-Gibert Fernandez, Joan, 1988-Orozco, Carlos AlbertoVinaixa Forner, Judith, 1991-Fillat i Fonts, CristinaViñals, FrancescNavarro Medrano, PilarPàncrees -- Càncer -- TractamentCurrent treatments for pancreatic ductal adenocarcinoma (PDA) are ineffective, making this the 4th leading cause of cancer deaths. Sunitinib is a broad-spectrum inhibitor of tyrosine kinase receptors mostly known for its anti-angiogenic effects. We tested the therapeutic effects of sunitinib in pancreatic cancer using the Ela-myc transgenic mouse model. We showed that Ela-myc pancreatic tumors express PDGFR and VEGFR in blood vessels and epithelial cells, rendering these tumors sensitive to sunitinib by more than only its anti-angiogenic activity. However, sunitinib treatment of Ela-myc mice with either early or advanced tumor progression had no impact on either survival or tumor burden. Further histopathological characterization of these tumors did not reveal differences in necrosis, cell differentiation, angiogenesis, apoptosis or proliferation. In stark contrast, in vitro sunitinib treatment of Ela-myc- derived cell lines showed high sensitivity to the drug, with increased apoptosis and reduced proliferation. Correspondingly, subcutaneous tumors generated from these cell lines completely regressed in vivo after sunitinib treatments. These data point at the pancreatic tumor microenvironment as the most likely barrier preventing sunitinib treatment efficiency in vivo. Combined treatments with drugs that disrupt tumor fibrosis may enhance sunitinib therapeutic effectiveness in pancreatic cancer treatment.Supported by Spanish Ministerio de Economía y Competitividad/ ISCIII-FEDER (PI14/00125), RETIC Cancer RD12/0036/0051/FEDER, and the “Generalitat de Catalunya” (2014/SGR/143) to P.N., and Spanish Ministerio de Economía y Competitividad/ISCIII-FEDER (BIO2014-57716-C2-2-R, IIS10/00014) to C.F.Impact Journals201620162016info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/27776http://dx.doi.org/10.18632/oncotarget.10199reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésOncotarget. 2016 Jul 26;7(30):48265-79All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.https://creativecommons.org/licenses/by/3.0/info:eu-repo/semantics/openAccessoai:recercat.cat:10230/277762026-05-29T05:05:01Z
dc.title.none.fl_str_mv	The pancreatic niche inhibits the effectiveness of sunitinib treatment of pancreatic cancer.
title	The pancreatic niche inhibits the effectiveness of sunitinib treatment of pancreatic cancer.
spellingShingle	The pancreatic niche inhibits the effectiveness of sunitinib treatment of pancreatic cancer. Martínez Bosch, Neus Pàncrees -- Càncer -- Tractament
title_short	The pancreatic niche inhibits the effectiveness of sunitinib treatment of pancreatic cancer.
title_full	The pancreatic niche inhibits the effectiveness of sunitinib treatment of pancreatic cancer.
title_fullStr	The pancreatic niche inhibits the effectiveness of sunitinib treatment of pancreatic cancer.
title_full_unstemmed	The pancreatic niche inhibits the effectiveness of sunitinib treatment of pancreatic cancer.
title_sort	The pancreatic niche inhibits the effectiveness of sunitinib treatment of pancreatic cancer.
dc.creator.none.fl_str_mv	Martínez Bosch, Neus Enrique Guerrero, Pedro Moreno, Mireia José Segarra-Martínez, Anabel Iglesias García, Mar Munné-Collado, Jessica Anta Rodríguez, Héctor, 1988- Gibert Fernandez, Joan, 1988- Orozco, Carlos Alberto Vinaixa Forner, Judith, 1991- Fillat i Fonts, Cristina Viñals, Francesc Navarro Medrano, Pilar
author	Martínez Bosch, Neus
author_facet	Martínez Bosch, Neus Enrique Guerrero, Pedro Moreno, Mireia José Segarra-Martínez, Anabel Iglesias García, Mar Munné-Collado, Jessica Anta Rodríguez, Héctor, 1988- Gibert Fernandez, Joan, 1988- Orozco, Carlos Alberto Vinaixa Forner, Judith, 1991- Fillat i Fonts, Cristina Viñals, Francesc Navarro Medrano, Pilar
author_role	author
author2	Enrique Guerrero, Pedro Moreno, Mireia José Segarra-Martínez, Anabel Iglesias García, Mar Munné-Collado, Jessica Anta Rodríguez, Héctor, 1988- Gibert Fernandez, Joan, 1988- Orozco, Carlos Alberto Vinaixa Forner, Judith, 1991- Fillat i Fonts, Cristina Viñals, Francesc Navarro Medrano, Pilar
author2_role	author author author author author author author author author author author author
dc.subject.none.fl_str_mv	Pàncrees -- Càncer -- Tractament
topic	Pàncrees -- Càncer -- Tractament
description	Current treatments for pancreatic ductal adenocarcinoma (PDA) are ineffective, making this the 4th leading cause of cancer deaths. Sunitinib is a broad-spectrum inhibitor of tyrosine kinase receptors mostly known for its anti-angiogenic effects. We tested the therapeutic effects of sunitinib in pancreatic cancer using the Ela-myc transgenic mouse model. We showed that Ela-myc pancreatic tumors express PDGFR and VEGFR in blood vessels and epithelial cells, rendering these tumors sensitive to sunitinib by more than only its anti-angiogenic activity. However, sunitinib treatment of Ela-myc mice with either early or advanced tumor progression had no impact on either survival or tumor burden. Further histopathological characterization of these tumors did not reveal differences in necrosis, cell differentiation, angiogenesis, apoptosis or proliferation. In stark contrast, in vitro sunitinib treatment of Ela-myc- derived cell lines showed high sensitivity to the drug, with increased apoptosis and reduced proliferation. Correspondingly, subcutaneous tumors generated from these cell lines completely regressed in vivo after sunitinib treatments. These data point at the pancreatic tumor microenvironment as the most likely barrier preventing sunitinib treatment efficiency in vivo. Combined treatments with drugs that disrupt tumor fibrosis may enhance sunitinib therapeutic effectiveness in pancreatic cancer treatment.
publishDate	2016
dc.date.none.fl_str_mv	2016 2016 2016
dc.type.none.fl_str_mv	info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion
format	article
status_str	publishedVersion
dc.identifier.none.fl_str_mv	http://hdl.handle.net/10230/27776 http://dx.doi.org/10.18632/oncotarget.10199
url	http://hdl.handle.net/10230/27776 http://dx.doi.org/10.18632/oncotarget.10199
dc.language.none.fl_str_mv	Inglés
language_invalid_str_mv	Inglés
dc.relation.none.fl_str_mv	Oncotarget. 2016 Jul 26;7(30):48265-79
dc.rights.none.fl_str_mv	https://creativecommons.org/licenses/by/3.0/ info:eu-repo/semantics/openAccess
rights_invalid_str_mv	https://creativecommons.org/licenses/by/3.0/
eu_rights_str_mv	openAccess
dc.format.none.fl_str_mv	application/pdf application/pdf
dc.publisher.none.fl_str_mv	Impact Journals
publisher.none.fl_str_mv	Impact Journals
dc.source.none.fl_str_mv	reponame:Recercat. Dipósit de la Recerca de Catalunya instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str	Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str	Recercat. Dipósit de la Recerca de Catalunya
collection	Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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The pancreatic niche inhibits the effectiveness of sunitinib treatment of pancreatic cancer.

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