{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T02:35:09Z","timestamp":1791167709799,"version":"4.1.0"},"reference-count":43,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2012,8,1]],"date-time":"2012-08-01T00:00:00Z","timestamp":1343779200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2012,9]]},"abstract":"<jats:p>Patients with triple\u2010negative breast cancers (<jats:styled-content style=\"fixed-case\">TNBC<\/jats:styled-content>s) typically have a poor prognosis because such cancers have no effective therapeutic targets, such as estrogen receptors for endocrine therapy or human epidermal growth factor receptor 2 (<jats:styled-content style=\"fixed-case\">HER<\/jats:styled-content>2) receptors for anti\u2010<jats:styled-content style=\"fixed-case\">HER<\/jats:styled-content>2 therapy. As the phosphatidylinositol 3\u2032 kinase (<jats:styled-content style=\"fixed-case\">PI<\/jats:styled-content>3<jats:styled-content style=\"fixed-case\">K<\/jats:styled-content>)\/<jats:styled-content style=\"fixed-case\">A<\/jats:styled-content>kt\/mammalian target of rapamycin (m<jats:styled-content style=\"fixed-case\">TOR<\/jats:styled-content>) cascade is activated in <jats:styled-content style=\"fixed-case\">TNBC<\/jats:styled-content>s, m<jats:styled-content style=\"fixed-case\">TOR<\/jats:styled-content> is a potential molecular target for anticancer therapy. In this study, we investigated the antitumor activities of everolimus, an oral m<jats:styled-content style=\"fixed-case\">TOR<\/jats:styled-content> inhibitor, in nine <jats:styled-content style=\"fixed-case\">TNBC<\/jats:styled-content> cell lines. Everolimus effectively inhibited cell growth at concentrations under 100\u00a0nM (<jats:styled-content style=\"fixed-case\">IC<\/jats:styled-content><jats:sub>50<\/jats:sub>) in five cell lines and even in the 1\u2010nM range in three of the five cell lines. To identify specific characteristics that could be used as predictive markers of efficacy, we evaluated the expressions of proteins in the m<jats:styled-content style=\"fixed-case\">TOR<\/jats:styled-content> cascade, basal markers, and cancer stem cell markers using western blotting, fluorescent <jats:italic>in situ<\/jats:italic> hybridization (<jats:styled-content style=\"fixed-case\">FISH<\/jats:styled-content>), or immunohistochemistry. All five of the sensitive cell lines were categorized as a basal\u2010like subtype positive for either epidermal growth factor receptor (<jats:styled-content style=\"fixed-case\">EGFR<\/jats:styled-content>) or <jats:styled-content style=\"fixed-case\">CK<\/jats:styled-content>5\/6, although resistant cell lines were not of this subtype and tended to exhibit the characteristics of cancer stem cells, with decreased <jats:styled-content style=\"fixed-case\">E<\/jats:styled-content>\u2010cadherin and the increased expression of <jats:styled-content style=\"fixed-case\">S<\/jats:styled-content>nail or <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>wist. <jats:italic>In vivo<\/jats:italic> assays demonstrated antitumor activity in a mouse xenograft model of basal\u2010like breast cancer, rather than non\u2010basal breast cancer. These results suggest that everolimus has favorable activity against basal\u2010like subtypes of <jats:styled-content style=\"fixed-case\">TNBC<\/jats:styled-content>s. Epidermal growth factor receptor and <jats:styled-content style=\"fixed-case\">CK<\/jats:styled-content>5\/6 are positive predictive markers of the <jats:styled-content style=\"fixed-case\">TNBC<\/jats:styled-content> response to everolimus, while cancer stem cell markers are negative predictive markers.<\/jats:p>","DOI":"10.1111\/j.1349-7006.2012.02359.x","type":"journal-article","created":{"date-parts":[[2012,6,17]],"date-time":"2012-06-17T22:05:28Z","timestamp":1339970728000},"page":"1665-1671","source":"Crossref","is-referenced-by-count":89,"title":["Efficacy of everolimus, a novel m<scp>TOR<\/scp> inhibitor, against basal\u2010like triple\u2010negative breast cancer cells"],"prefix":"10.1111","volume":"103","author":[{"given":"Mayu","family":"Yunokawa","sequence":"first","affiliation":[{"name":"Department of Breast and Medical Oncology National Cancer Center Hospital Tokyo 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