1. DIGITAL.CSIC
  2. Biología y Biomedicina
  3. Instituto de Biología Molecular y Celular del Cáncer de Salamanca (IBMCC)
  4. (IBMCC) Artículos
Por favor, use este identificador para citar o enlazar a este item: http://hdl.handle.net/10261/135763
COMPARTIR / EXPORTAR:
logo share SHARE logo core CORE BASE

Comparte tu historia
de Acceso Abierto
Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL | DATACITE

Invitar a revisión por pares abierta
Campo DC Valor Lengua/Idioma
dc.contributor.authorOrdóñez, José Luis-
dc.contributor.authorAmaral, Ana Teresa-
dc.contributor.authorHerrero-Martín, David-
dc.contributor.authorGarcía-Macías, Carmen-
dc.contributor.authorSevillano, Victoria-
dc.contributor.authorSan-Segundo, Laura-
dc.contributor.authorFraile, Susana-
dc.contributor.authorTeodosio, Cristina-
dc.contributor.authorTirado, Óscar M.-
dc.contributor.authorMora, Jaume-
dc.contributor.authorÁlava, Enrique de-
dc.date.accessioned2016-08-23T07:41:28Z-
dc.date.available2016-08-23T07:41:28Z-
dc.date.issued2015-
dc.identifierdoi: 10.18632/oncotarget.4303-
dc.identifiere-issn: 1949-2553-
dc.identifier.citationOncotarget 6(22): 18875-18890 (2015)-
dc.identifier.urihttp://hdl.handle.net/10261/135763-
dc.descriptionThis is an open-access article distributed under the terms of the Creative Commons Attribution License.-- et al.-
dc.description.abstractRecent preclinical evidence has suggested that Ewing Sarcoma (ES) bearing EWSR1-ETS fusions could be particularly sensitive to PARP inhibitors (PARPinh) in combination with DNA damage repair (DDR) agents. Trabectedin is an antitumoral agent that modulates EWSR1-FLI1 transcriptional functions, causing DNA damage. Interestingly, PARP1 is also a transcriptional regulator of EWSR1-FLI1, and PARPinh disrupts the DDR machinery. Thus, given the impact and apparent specificity of both agents with regard to the DNA damage/DDR system and EWSR1-FLI1 activity in ES, we decided to explore the activity of combining PARPinh and Trabectedin in in vitro and in vivo experiments. The combination of Olaparib and Trabectedin was found to be highly synergistic, inhibiting cell proliferation, inducing apoptosis, and the accumulation of G2/M. The drug combination also enhanced γH2AX intranuclear accumulation as a result of DNA damage induction, DNA fragmentation and global DDR deregulation, while EWSR1-FLI1 target expression remained unaffected. The effect of the drug combination was corroborated in a mouse xenograft model of ES and, more importantly, in two ES patient-derived xenograft (PDX) models in which the tumors showed complete regression. In conclusion, the combination of the two agents leads to a biologically significant deregulation of the DDR machinery that elicits relevant antitumor activity in preclinical models and might represent a promising therapeutic tool that should be further explored for translation to the clinical setting.-
dc.description.sponsorshipEnrique de Álava’s lab is supported by the AECC (Asociación Española Contra el Cáncer), the Ministry of Economy and Competitiveness of Spain-FEDER (PI081828, RD06/0020/0059 RD12/0036/0017, PT13/0010/0056, PI110018, ISCIII Sara Borrell postdoc grant CD06/00001), the European Project EuroSARC (FP7-HEALTH-2011- two-stage, Project ID 278742 EUROSARC), Fundación Memoria de D. Manuel Solorzano Barruso, Fundación Cris contra el cancer, and Fundación María García Estrada. JLO was sponsored by the CSIC and the European Social Fund (post-doctoral grant JAE DOC) and is at present funded by the AECC. ATA is sponsored by the Fundaçao para a Ciência e Tecnologia, Portugal (fellowship SFRH/BD/69318/2010). OMT is funded by Fondo de Investigaciones Sanitarias-ISCIII (CES12/021) and the AECC. DHM is funded by the AECC. Work supported by the Xarxa de Bancs de Tumors de Catalunya (XBTC) sponsored by Pla Director d’Oncologia de Catalunya. AMC acknowledges funding from the European Union Seventh Framework Programme (FP7/2007-2013) under a Marie Curie International Reintegration Grant (PIRG-08- GA-2010-276998) and ISCIII-FEDER (CP13/00189).-
dc.publisherImpact Journals-
dc.relationinfo:eu-repo/grantAgreement/EC/FP7/278742-
dc.relationinfo:eu-repo/grantAgreement/EC/FP7/276998-
dc.relation.isversionofPublisher's version-
dc.rightsopenAccess-
dc.subjectPDX models-
dc.subjectDNA damage-
dc.subjectTrabectedin-
dc.subjectPARP inhibitor-
dc.subjectEwing sarcoma-
dc.titleThe PARP inhibitor olaparib enhances the sensitivity of Ewing sarcoma to trabectedin-
dc.typeartículo-
dc.identifier.doi10.18632/oncotarget.4303-
dc.relation.publisherversionhttp://dx.doi.org/10.18632/oncotarget.4303-
dc.date.updated2016-08-23T07:41:29Z-
dc.description.versionPeer Reviewed-
dc.language.rfc3066eng-
dc.rights.licensehttp://creativecommons.org/licenses/by/3.0/-
dc.contributor.funderGeneralitat de Catalunya-
dc.contributor.funderXarxa de Bancs de Tumors de Catalunya-
dc.contributor.funderFederación Española de Enfermedades Raras-
dc.contributor.funderConsejo Superior de Investigaciones Científicas (España)-
dc.contributor.funderEuropean Commission-
dc.contributor.funderFundación Memoria de D. Samuel Solorzano Barruso-
dc.contributor.funderInstituto de Salud Carlos III-
dc.contributor.funderMinisterio de Economía y Competitividad (España)-
dc.contributor.funderAsociación Española Contra el Cáncer-
dc.contributor.funderFundación CRIS contra el Cáncer-
dc.relation.csicSí-
dc.identifier.funderhttp://dx.doi.org/10.13039/501100002809es_ES
dc.identifier.funderhttp://dx.doi.org/10.13039/501100002924es_ES
dc.identifier.funderhttp://dx.doi.org/10.13039/501100003339es_ES
dc.identifier.funderhttp://dx.doi.org/10.13039/501100000780es_ES
dc.identifier.funderhttp://dx.doi.org/10.13039/501100004587es_ES
dc.identifier.funderhttp://dx.doi.org/10.13039/501100003329es_ES
dc.identifier.pmid26056084-
dc.type.coarhttp://purl.org/coar/resource_type/c_6501es_ES
item.openairetypeartículo-
item.fulltextWith Fulltext-
item.grantfulltextopen-
item.cerifentitytypePublications-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
Aparece en las colecciones: (IBIS) Artículos
(IBMCC) Artículos
Ficheros en este ítem:
Fichero Descripción Tamaño Formato
Ewing sarcoma to trabectedin.pdf2,54 MBAdobe PDFVista previa
Visualizar/Abrir
Show simple item record

CORE Recommender

PubMed Central
Citations

41
checked on 06-may-2024

SCOPUSTM   
Citations

68
checked on 10-may-2024

WEB OF SCIENCETM
Citations

59
checked on 23-feb-2024

Page view(s)

378
checked on 11-may-2024

Download(s)

357
checked on 11-may-2024

Google ScholarTM

Check

Altmetric

Altmetric


Artículos relacionados:


Este item está licenciado bajo una Licencia Creative Commons Creative Commons