The pancreatic niche inhibits the effectiveness of sunitinib treatment of pancreatic cancer.
Mostra el registre complet Registre parcial de l'ítem
- dc.contributor.author Martínez Bosch, Neusca
- dc.contributor.author Enrique Guerrero, Pedroca
- dc.contributor.author Moreno, Mireiaca
- dc.contributor.author José Segarra-Martínez, Anabelca
- dc.contributor.author Iglesias García, Marca
- dc.contributor.author Munné-Collado, Jessicaca
- dc.contributor.author Anta Rodríguez, Héctor, 1988-ca
- dc.contributor.author Gibert, Joanca
- dc.contributor.author Orozco, Carlos Albertoca
- dc.contributor.author Vinaixa Forner, Judith, 1991-ca
- dc.contributor.author Fillat i Fonts, Cristinaca
- dc.contributor.author Viñals, Francescca
- dc.contributor.author Navarro Medrano, Pilarca
- dc.date.accessioned 2016-12-15T11:31:16Z
- dc.date.available 2016-12-15T11:31:16Z
- dc.date.issued 2016
- dc.description.abstract 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.ca
- dc.description.sponsorship 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.
- dc.format.mimetype application/pdfca
- dc.identifier.citation Martínez-Bosch N, Guerrero PE, Moreno M, José A, Iglesias M, Munné-Collado J. et al. The pancreatic niche inhibits the effectiveness of sunitinib treatment of pancreatic cancer. Oncotarget. 2016 Jul 26;7(30):48265-48279. doi: 10.18632/oncotarget.10199ca
- dc.identifier.doi http://dx.doi.org/10.18632/oncotarget.10199
- dc.identifier.issn 1949-2553
- dc.identifier.uri http://hdl.handle.net/10230/27776
- dc.language.iso engca
- dc.publisher Impact Journalsca
- dc.relation.ispartof Oncotarget. 2016 Jul 26;7(30):48265-79
- dc.rights All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.ca
- dc.rights.accessRights info:eu-repo/semantics/openAccessca
- dc.rights.uri https://creativecommons.org/licenses/by/3.0/ca
- dc.subject.other Pàncrees -- Càncer -- Tractamentca
- dc.title The pancreatic niche inhibits the effectiveness of sunitinib treatment of pancreatic cancer.ca
- dc.type info:eu-repo/semantics/articleca
- dc.type.version info:eu-repo/semantics/publishedVersionca