dc.contributor.author | Nieto-Soler, Maria | |
dc.contributor.author | Morgado-Palacin, Isabel | |
dc.contributor.author | Lafarga, Vanesa | |
dc.contributor.author | Lecona, Emilio | |
dc.contributor.author | Murga, Matilde | |
dc.contributor.author | Callen, Elsa | |
dc.contributor.author | Azorin, Daniel | |
dc.contributor.author | Alonso, Javier | |
dc.contributor.author | Lopez-Contreras, Andres J | |
dc.contributor.author | Nussenzweig, Andre | |
dc.contributor.author | Fernandez-Capetillo, Oscar | |
dc.date.accessioned | 2020-04-17T16:09:00Z | |
dc.date.available | 2020-04-17T16:09:00Z | |
dc.date.issued | 2016-09-13 | |
dc.identifier.citation | Oncotarget. 2016 Sep 13;7(37):58759-58767. | es_ES |
dc.identifier.issn | 1949-2553 | es_ES |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/9615 | |
dc.description.abstract | Ewing sarcomas (ES) are pediatric bone tumors that arise from a driver translocation, most frequently EWS/FLI1. Current ES treatment involves DNA damaging agents, yet the basis for the sensitivity to these therapies remains unknown. Oncogene-induced replication stress (RS) is a known source of endogenous DNA damage in cancer, which is suppressed by ATR and CHK1 kinases. We here show that ES suffer from high endogenous levels of RS, rendering them particularly dependent on the ATR pathway. Accordingly, two independent ATR inhibitors show in vitro toxicity in ES cell lines as well as in vivo efficacy in ES xenografts as single agents. Expression of EWS/FLI1 or EWS/ERG oncogenic translocations sensitizes non-ES cells to ATR inhibitors. Our data shed light onto the sensitivity of ES to genotoxic agents, and identify ATR inhibitors as a potential therapy for Ewing Sarcomas. | es_ES |
dc.description.sponsorship | We would want to thank Enrique de Alava for providing ES lines. Work in O.F. laboratory was supported by Fundación Botín, by Banco Santander through its Santander Universities Global Division and by grants from MINECO (SAF2014-57791-REDC and SAF2014-59498-R), Fundació La Marato de TV3, Howard Hughes Medical Institute and the European Research Council (ERC-617840). The A.N. laboratory was supported by the Intramural Research Program of the NIH, the National Cancer Institute, the Center for Cancer Research, an Ellison Medical Foundation Senior Scholar in Aging, and the Alex Lemonade Stand Foundation Award. J.A. laboratory is supported by Asociación Pablo Ugarte, ASION-La Hucha de Tomás, Fundación La Sonrisa de Alex and Instituto de Salud Carlos III (PI12/00816 and Spanish Cancer Network RTICC RD12/0036/0027). A.L. laboratory was supported by the Danish National Research Foundation (DNRF115), Danish Council for Independent Research (Sapere Aude, DFF-Starting Grant 2014) and Danish Cancer Society (KBVU-2014). | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Impact Journals | es_ES |
dc.type.hasVersion | VoR | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.subject | ATR | es_ES |
dc.subject | DNA repair | es_ES |
dc.subject | Ewing sarcoma | es_ES |
dc.subject | cancer | es_ES |
dc.subject | replication stress | es_ES |
dc.subject.mesh | Animals | es_ES |
dc.subject.mesh | Antineoplastic Agents | es_ES |
dc.subject.mesh | Apoptosis | es_ES |
dc.subject.mesh | Ataxia Telangiectasia Mutated Proteins | es_ES |
dc.subject.mesh | Bone Neoplasms | es_ES |
dc.subject.mesh | Cell Line, Tumor | es_ES |
dc.subject.mesh | DNA Damage | es_ES |
dc.subject.mesh | Gene Expression Regulation, Neoplastic | es_ES |
dc.subject.mesh | Humans | es_ES |
dc.subject.mesh | Male | es_ES |
dc.subject.mesh | Mice | es_ES |
dc.subject.mesh | Mice, SCID | es_ES |
dc.subject.mesh | RNA, Small Interfering | es_ES |
dc.subject.mesh | RNA-Binding Protein EWS | es_ES |
dc.subject.mesh | Sarcoma, Ewing | es_ES |
dc.title | Efficacy of ATR inhibitors as single agents in Ewing sarcoma | es_ES |
dc.type | journal article | es_ES |
dc.rights.license | Atribución 4.0 Internacional | * |
dc.identifier.pubmedID | 27577084 | es_ES |
dc.format.volume | 7 | es_ES |
dc.format.number | 37 | es_ES |
dc.format.page | 58759-58767 | es_ES |
dc.identifier.doi | 10.18632/oncotarget.11643 | es_ES |
dc.contributor.funder | Banco Santander | |
dc.contributor.funder | Ministerio de Economía y Competitividad (España) | |
dc.contributor.funder | Fundación La Marató TV3 | |
dc.contributor.funder | Howard Hughes Medical Institute | |
dc.contributor.funder | Instituto de Salud Carlos III | |
dc.contributor.funder | Red Temática de Investigación Cooperativa en Cáncer (RTICC) (España) | |
dc.description.peerreviewed | Sí | es_ES |
dc.identifier.e-issn | 1949-2553 | es_ES |
dc.relation.publisherversion | https://doi.org/10.18632/oncotarget.11643 | es_ES |
dc.identifier.journal | Oncotarget | es_ES |
dc.repisalud.centro | ISCIII::Instituto de Investigación de Enfermedades Raras | es_ES |
dc.repisalud.institucion | ISCIII | es_ES |
dc.relation.projectID | info:eu_repo/grantAgreement/ES/SAF2014-57791-REDC | es_ES |
dc.relation.projectID | info:eu_repo/grantAgreement/ES/SAF2014-59498-R | es_ES |
dc.relation.projectID | info:eu_repo/grantAgreement/ES/ERC-617840 | es_ES |
dc.relation.projectID | info:eu_repo/grantAgreement/ES/RTICC RD12/0036/0027 | es_ES |
dc.relation.projectID | info:eu_repo/grantAgreement/ES/DNRF115 | es_ES |
dc.relation.projectID | info:eu_repo/grantAgreement/ES/KBVU-2014 | es_ES |
dc.rights.accessRights | open access | es_ES |