dc.creator | Perez, Marco | es |
dc.creator | Lucena Cacace, Antonio | es |
dc.creator | Marín Gómez, Luis Miguel | es |
dc.creator | Padillo Ruiz, Francisco Javier | es |
dc.creator | Robles Frias, MJ | es |
dc.creator | Saez, Carmen | es |
dc.creator | García Carbonero, Rocío | es |
dc.creator | Carnero Moya, Amancio | es |
dc.date.accessioned | 2020-04-29T16:30:12Z | |
dc.date.available | 2020-04-29T16:30:12Z | |
dc.date.issued | 2016-04-20 | |
dc.identifier.citation | Perez, M., Lucena Cacace, A., Marín Gómez, L.M., Padillo Ruiz, F.J., Robles Frias, M., Saez, C.,...,Carnero Moya, A. (2016). Dasatinib, a Src inhibitor, sensitizes liver metastatic colorectal carcinoma to oxaliplatin in tumors with high levels of phospho-Src.. Oncotarget, 7 (22), 33111-33124. | |
dc.identifier.issn | 1949-2553 | es |
dc.identifier.uri | https://hdl.handle.net/11441/95985 | |
dc.description.abstract | Despite the development of new antineoplastic agents for the treatment of
colorectal cancer (CRC), oxaliplatin and fluoropyrimidines remain the most commonly
employed drugs for the treatment of both early and advanced disease. Intrinsic or
acquired resistance is, however, an important limitation to pharmacological therapy,
and the development of chemosensitization strategies constitute a major goal
with important clinical implications. In the present work, we determined that high
levels of activated Src kinase, measured as phospho-Src at the Tyr419 residue in
CRC cell lines, can promote colorectal carcinoma cell resistance to oxaliplatin, but
not to 5-fluorouracil (5FU), and that inhibition of this protein restores sensitivity to
oxaliplatin. Similar results were observed with in vivo patient-derived xenograft (PDX)
models that were orthotopically grown in murine livers. In PDX tumor lines derived
from human CRC liver metastasis, dasatinib, a Src inhibitor, increases sensitivity
to oxaliplatin only in tumors with high p-Src. However, dasatinib did not modify
sensitivity to 5FU in any of the models. Our data suggest that chemoresistance
induced by p-Src is specific to oxaliplatin, and that p-Src levels can be used to identify
patients who may benefit from this combination therapy. These results are relevant
for clinicians as they identify a novel biomarker of drug resistance that is suitable to
pharmacological manipulation. | es |
dc.description.sponsorship | HUVR-IBiS Biobanco del Sistema Sanitario Público de Andalucía y ISCIII-Red de Biobancos [PT13/0010/0056]. | es |
dc.description.sponsorship | FEDER from Regional Development European Funds (European Union), Ministerio de Economía y Competitividad, Plan Nacional de I+D+I 2008-2011, Plan Estatal de I+D+i 2013-2016, ISCIII [Fis: PI12/00137, PI13/02295, PI15/00045, RTICC: RD12/0036/0028]. | es |
dc.description.sponsorship | Consejería de Ciencia e Innovación [CTS-1848] y Consejería de Salud de la Junta de Andalucía [PI-0306-2012, PI-0096-2014]. | es |
dc.format | application/pdf | es |
dc.format.extent | 15 | es |
dc.language.iso | eng | es |
dc.publisher | Impact Journals | es |
dc.relation.ispartof | Oncotarget, 7 (22), 33111-33124. | |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.subject | Metastatic colorectal carcinoma | es |
dc.subject | Cancer treatment | es |
dc.subject | Src kinase | es |
dc.subject | Biomarkers | es |
dc.subject | Pdx models | es |
dc.title | Dasatinib, a Src inhibitor, sensitizes liver metastatic colorectal carcinoma to oxaliplatin in tumors with high levels of phospho-Src. | 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 | Universidad de Sevilla. Departamento de Cirugía | es |
dc.contributor.affiliation | Universidad de Sevilla. Departamento de Medicina | es |
dc.identifier.doi | 10.18632/oncotarget.8880 | es |
dc.contributor.group | Universidad de Sevilla. CTS664: Cirugía avanzada y trasplantes. Terapia celular y bioingeniería aplicada a la cirugía. | es |
dc.journaltitle | Oncotarget | es |
dc.publication.volumen | 7 | es |
dc.publication.issue | 22 | es |
dc.publication.initialPage | 33111 | es |
dc.publication.endPage | 33124 | es |