Pharmacologic inhibition of ATR and ATM offers clinically important distinctions to enhancing platinum or radiation response in ovarian, endometrial, and cervical cancer cells.
Pharmacologic inhibition of ATR and ATM offers clinically important distinctions to enhancing platinum or radiation response in ovarian, endometrial, and cervical cancer cells.
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DOI：
10.1016/j.ygyno.2014.12.035
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发表时间：
2015-03
影响因子：
4.7
通讯作者：
Conrads TP
中科院分区：
文献类型：
--
作者：
Teng PN;Bateman NW;Darcy KM;Hamilton CA;Maxwell GL;Bakkenist CJ;Conrads TP
Significant reductions in gynecologic (GYN) cancer mortality and morbidity require treatments that prevent and reverse resistance to chemotherapy and radiation. The objective of this study was to determine if pharmacologic inhibition of key DNA damage response kinases in GYN cancers would enhance cell killing by platinum-based chemotherapy and radiation. A panel of human ovarian, endometrial and cervical cancer cell lines were treated with platinum drugs or ionizing radiation (IR) along with small molecule pharmacological kinase inhibitors of Ataxia telangiectasia mutated (ATM) and ATM and Rad-3-related (ATR). Pharmacologic inhibition of ATR significantly enhanced platinum drug response in all GYN cancer cell lines tested, whereas inhibition of ATM did not enhance the response to platinum drugs. Co-inhibition of ATM and ATR did not enhance platinum kill beyond that observed by inhibition of ATR alone. By contrast, inhibiting either ATR or ATM enhanced the response to IR in all GYN cancer cells, with further enhancement achieved with co-inhibition. These studies highlight actionable mechanisms operative in GYN cancer cells with potential to maximize response of platinum agents and radiation in newly diagnosed as well as recurrent gynecologic cancers.
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DOI：
10.1158/1078-0432.ccr-12-3408
发表时间：
2013-06-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Biddlestone-Thorpe L;Sajjad M;Rosenberg E;Beckta JM;Valerie NC;Tokarz M;Adams BR;Wagner AF;Khalil A;Gilfor D;Golding SE;Deb S;Temesi DG;Lau A;O'Connor MJ;Choe KS;Parada LF;Lim SK;Mukhopadhyay ND;Valerie K
通讯作者：
Valerie K
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
6.4
作者：
Chen, Zehan;Xiao, Zhan;Zhang, Haiying
通讯作者：
Zhang, Haiying
影响因子：
21.3
作者：
Jazayeri, A;Falck, J;Jackson, SP
通讯作者：
Jackson, SP
影响因子：
4.7
作者：
Arora, Shilpi;Bisanz, Kristen M.;Azorsa, David O.
通讯作者：
Azorsa, David O.