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dc.contributor.authorNieto-Soler, Maria
dc.contributor.authorMorgado-Palacin, Isabel
dc.contributor.authorLafarga, Vanesa 
dc.contributor.authorLecona, Emilio
dc.contributor.authorMurga M, Murga M 
dc.contributor.authorCallen, Elsa
dc.contributor.authorAzorin, Daniel
dc.contributor.authorAlonso, Javier 
dc.contributor.authorLopez-Contreras, Andres J
dc.contributor.authorNussenzweig, Andre
dc.contributor.authorFernandez-Capetillo, Oscar 
dc.date.accessioned2020-04-17T16:09:00Z
dc.date.available2020-04-17T16:09:00Z
dc.date.issued2016-09-13
dc.identifier.citationOncotarget. 2016 Sep 13;7(37):58759-58767.es_ES
dc.identifier.issn1949-2553es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/9615
dc.description.abstractEwing 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.sponsorshipWe 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.isoenges_ES
dc.publisherImpact Journalses_ES
dc.relation.isversionofPublisher's versiones_ES
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectATRes_ES
dc.subjectDNA repaires_ES
dc.subjectEwing sarcomaes_ES
dc.subjectcanceres_ES
dc.subjectreplication stresses_ES
dc.subject.meshAnimals es_ES
dc.subject.meshAntineoplastic Agents es_ES
dc.subject.meshApoptosis es_ES
dc.subject.meshAtaxia Telangiectasia Mutated Proteins es_ES
dc.subject.meshBone Neoplasms es_ES
dc.subject.meshCell Line, Tumor es_ES
dc.subject.meshDNA Damage es_ES
dc.subject.meshGene Expression Regulation, Neoplastic es_ES
dc.subject.meshHumans es_ES
dc.subject.meshMale es_ES
dc.subject.meshMice es_ES
dc.subject.meshMice, SCID es_ES
dc.subject.meshRNA, Small Interfering es_ES
dc.subject.meshRNA-Binding Protein EWS es_ES
dc.subject.meshSarcoma, Ewing es_ES
dc.titleEfficacy of ATR inhibitors as single agents in Ewing sarcomaes_ES
dc.typeArtículoes_ES
dc.rights.licenseAtribución 4.0 Internacional*
dc.identifier.pubmedID27577084es_ES
dc.format.volume7es_ES
dc.format.number37es_ES
dc.format.page58759-58767es_ES
dc.identifier.doi10.18632/oncotarget.11643es_ES
dc.contributor.funderBanco Santanderes_ES
dc.contributor.funderMinisterio de Economía y Competitividad (España)es_ES
dc.contributor.funderFundación La Mataró TV3es_ES
dc.contributor.funderHoward Hughes Medical Institutees_ES
dc.contributor.funderInstituto de Salud Carlos III - ISCIIIes_ES
dc.contributor.funderRed Temática de Investigación Cooperativa en Cáncer (España)es_ES
dc.description.peerreviewedes_ES
dc.identifier.e-issn1949-2553es_ES
dc.relation.publisherversionhttps://doi.org/10.18632/oncotarget.11643es_ES
dc.identifier.journalOncotargetes_ES
dc.repisalud.centroISCIII::Instituto de Investigación de Enfermedades Rarases_ES
dc.repisalud.institucionISCIIIes_ES
dc.relation.projectIDinfo:eu_repo/grantAgreement/ES/SAF2014-57791-REDCes_ES
dc.relation.projectIDinfo:eu_repo/grantAgreement/ES/SAF2014-59498-Res_ES
dc.relation.projectIDinfo:eu_repo/grantAgreement/ES/ERC-617840es_ES
dc.relation.projectIDinfo:eu_repo/grantAgreement/ES/RTICC RD12/0036/0027es_ES
dc.relation.projectIDinfo:eu_repo/grantAgreement/ES/DNRF115es_ES
dc.relation.projectIDinfo:eu_repo/grantAgreement/ES/KBVU-2014es_ES
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses_ES


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Atribución 4.0 Internacional
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