2026-06-14T03:33:22Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/96152025-06-17T10:22:10Zcom_20.500.12105_2173com_20.500.12105_2051com_20.500.12105_2052col_20.500.12105_19597col_20.500.12105_19616
Repisalud
author
Nieto-Soler, Maria
author
Morgado-Palacin, Isabel
author
Lafarga, Vanesa
author
Lecona, Emilio
author
Murga, Matilde
author
Callen, Elsa
author
Azorin, Daniel
author
Alonso, Javier
author
Lopez-Contreras, Andres J
author
Nussenzweig, Andre
author
Fernandez-Capetillo, Oscar
funder
Banco Santander
funder
Ministerio de Economía y Competitividad (España)
funder
Fundación La Marató TV3
funder
Howard Hughes Medical Institute
funder
Instituto de Salud Carlos III
funder
Red Temática de Investigación Cooperativa en Cáncer (RTICC) (España)
2020-04-17T16:09:00Z
2020-04-17T16:09:00Z
2016-09-13
Oncotarget. 2016 Sep 13;7(37):58759-58767.
10.18632/oncotarget.11643
1949-2553
1949-2553
Oncotarget
27577084
http://hdl.handle.net/20.500.12105/9615
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.
eng
ATR
DNA repair
Ewing sarcoma
Cancer
Replication stress
Efficacy of ATR inhibitors as single agents in Ewing sarcoma
research article
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URL
https://repisalud.isciii.es/bitstreams/05f56ba1-f433-4aea-b796-8d2920af64b5/download
File
MD5
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application/pdf
EfficacyOfATRInhibitors_2016.pdf
URL
https://repisalud.isciii.es/bitstreams/34cba3ea-2c99-49ef-a407-daf3ca33cf21/download
File
MD5
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text/plain
EfficacyOfATRInhibitors_2016.pdf.txt