Efficacy of ATR inhibitors as single agents in Ewing sarcoma

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Efficacy of ATR inhibitors as single agents in Ewing sarcoma. / Nieto-Soler, Maria; Morgado-Palacin, Isabel; Lafarga, Vanesa; Lecona, Emilio; Murga, Matilde; Callen, Elsa; Azorin, Daniel; Alonso, Javier; Lopez-Contreras, Andres J.; Nussenzweig, Andre; Fernandez-Capetillo, Oscar.

In: OncoTarget, Vol. 7, No. 37, 26.08.2016, p. 58759-58767.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Nieto-Soler, M, Morgado-Palacin, I, Lafarga, V, Lecona, E, Murga, M, Callen, E, Azorin, D, Alonso, J, Lopez-Contreras, AJ, Nussenzweig, A & Fernandez-Capetillo, O 2016, 'Efficacy of ATR inhibitors as single agents in Ewing sarcoma', OncoTarget, vol. 7, no. 37, pp. 58759-58767. https://doi.org/10.18632/oncotarget.11643

APA

Nieto-Soler, M., Morgado-Palacin, I., Lafarga, V., Lecona, E., Murga, M., Callen, E., Azorin, D., Alonso, J., Lopez-Contreras, A. J., Nussenzweig, A., & Fernandez-Capetillo, O. (2016). Efficacy of ATR inhibitors as single agents in Ewing sarcoma. OncoTarget, 7(37), 58759-58767. https://doi.org/10.18632/oncotarget.11643

Vancouver

Nieto-Soler M, Morgado-Palacin I, Lafarga V, Lecona E, Murga M, Callen E et al. Efficacy of ATR inhibitors as single agents in Ewing sarcoma. OncoTarget. 2016 Aug 26;7(37):58759-58767. https://doi.org/10.18632/oncotarget.11643

Author

Nieto-Soler, Maria ; Morgado-Palacin, Isabel ; Lafarga, Vanesa ; Lecona, Emilio ; Murga, Matilde ; Callen, Elsa ; Azorin, Daniel ; Alonso, Javier ; Lopez-Contreras, Andres J. ; Nussenzweig, Andre ; Fernandez-Capetillo, Oscar. / Efficacy of ATR inhibitors as single agents in Ewing sarcoma. In: OncoTarget. 2016 ; Vol. 7, No. 37. pp. 58759-58767.

Bibtex

@article{d45f55798da64f88893c4845484019bf,
title = "Efficacy of ATR inhibitors as single agents in Ewing sarcoma",
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.",
keywords = "ATR, Ewing sarcoma, replication stress, DNA repair, cancer",
author = "Maria Nieto-Soler and Isabel Morgado-Palacin and Vanesa Lafarga and Emilio Lecona and Matilde Murga and Elsa Callen and Daniel Azorin and Javier Alonso and Lopez-Contreras, {Andres J.} and Andre Nussenzweig and Oscar Fernandez-Capetillo",
year = "2016",
month = aug,
day = "26",
doi = "10.18632/oncotarget.11643",
language = "English",
volume = "7",
pages = "58759--58767",
journal = "Oncotarget",
issn = "1949-2553",
publisher = "Impact Journals LLC",
number = "37",

}

RIS

TY - JOUR

T1 - Efficacy of ATR inhibitors as single agents in Ewing sarcoma

AU - Nieto-Soler, Maria

AU - Morgado-Palacin, Isabel

AU - Lafarga, Vanesa

AU - Lecona, Emilio

AU - Murga, Matilde

AU - Callen, Elsa

AU - Azorin, Daniel

AU - Alonso, Javier

AU - Lopez-Contreras, Andres J.

AU - Nussenzweig, Andre

AU - Fernandez-Capetillo, Oscar

PY - 2016/8/26

Y1 - 2016/8/26

N2 - 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.

AB - 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.

KW - ATR

KW - Ewing sarcoma

KW - replication stress

KW - DNA repair

KW - cancer

U2 - 10.18632/oncotarget.11643

DO - 10.18632/oncotarget.11643

M3 - Journal article

C2 - 27577084

VL - 7

SP - 58759

EP - 58767

JO - Oncotarget

JF - Oncotarget

SN - 1949-2553

IS - 37

ER -

ID: 169441305