{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T23:10:55Z","timestamp":1793661055114,"version":"4.5.1"},"reference-count":32,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2016,10,21]],"date-time":"2016-10-21T00:00:00Z","timestamp":1477008000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003710","name":"Korea Health Industry Development Institute","doi-asserted-by":"publisher","award":["HI14C1277"],"award-info":[{"award-number":["HI14C1277"]}],"id":[{"id":"10.13039\/501100003710","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2017,1]]},"abstract":"<jats:p>Ataxia telangiectasia and Rad3\u2010related (ATR) proteins are sensors of DNA damage, which induces homologous recombination (HR)\u2010dependent repair. ATR is a master regulator of DNA damage repair (DDR), signaling to control DNA replication, DNA repair and apoptosis. Therefore, the ATR pathway might be an attractive target for developing new drugs. This study was designed to investigate the antitumor effects of the ATR inhibitor, AZD6738 and its underlying mechanism in human breast cancer cells. Growth inhibitory effects of AZD6738 against human breast cancer cell lines were studied using a 3\u2010(4,5\u2010dimethylthiazol\u20102\u2010yl)\u22122,5\u2010diphenyltetrazolium bromide (methyl thiazolyl tetrazolium, MTT) assay. Cell cycle analysis, Western blotting, immunofluorescence and comet assays were also performed to elucidate underlying mechanisms of AZD6738 action. Anti\u2010proliferative and DDR inhibitory effects of AZD6738 were demonstrated in human breast cancer cell lines. Among 13 cell lines, the IC<jats:sub>50<\/jats:sub> values of nine cell lines were less than 1 \u03bcmol\/L using MTT assay. Two cell lines, SK\u2010BR\u20103 and BT\u2010474, were chosen for further evaluation focused on human epidermal growth factor receptor 2 (HER2)\u2010positive breast cancer cells. Sensitive SK\u2010BR\u20103 but not the less sensitive BT\u2010474 breast cancer cells showed increased level of apoptosis and S phase arrest and reduced expression levels of phosphorylated check\u2010point kinase 1 (CHK1) and other repair markers. Decreased functional CHK1 expression induced DNA damage accumulation due to HR inactivation. AZD6738 showed synergistic activity with cisplatin. Understanding the antitumor activity and mechanisms of AZD6738 in HER2\u2010positive breast cancer cells creates the possibility for future clinical trials targeting DDR in HER2\u2010positive breast cancer treatment.<\/jats:p>","DOI":"10.1002\/ijc.30373","type":"journal-article","created":{"date-parts":[[2016,8,8]],"date-time":"2016-08-08T19:27:12Z","timestamp":1470684432000},"page":"109-119","source":"Crossref","is-referenced-by-count":58,"title":["Anti\u2010tumor activity of the ATR inhibitor AZD6738 in HER2 positive breast cancer cells"],"prefix":"10.1002","volume":"140","author":[{"given":"Hee\u2010Jun","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Internal Medicine Chung\u2010Ang University College of Medicine  Seoul Korea"},{"name":"Translational Medicine Seoul National University College of Medicine  Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahrum","family":"Min","sequence":"additional","affiliation":[{"name":"Cancer 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