{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T12:04:25Z","timestamp":1791201865692,"version":"4.2.0"},"reference-count":49,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2012,3,27]],"date-time":"2012-03-27T00:00:00Z","timestamp":1332806400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["accpjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacotherapy"],"published-print":{"date-parts":[[2012,4]]},"abstract":"<jats:p>\n                    The mammalian target of rapamycin (\n                    <jats:styled-content style=\"fixed-case\">mTOR<\/jats:styled-content>\n                    ) is a signaling kinase of the phosphatidylinositol 3\u2010kinase\/protein kinase\n                    <jats:styled-content style=\"fixed-case\">B<\/jats:styled-content>\n                    (also known as Akt) signaling pathway that mediates cell growth and metabolism. Dysregulation of the\n                    <jats:styled-content style=\"fixed-case\">mTOR<\/jats:styled-content>\n                    pathway creates a favorable environment for the development and progression of many cancers, including breast cancer, and is associated with the development of resistance to endocrine therapy and to the anti\u2013human epidermal growth factor receptor\u20102 (HER2) monoclonal antibody trastuzumab. Therefore, the addition of\n                    <jats:styled-content style=\"fixed-case\">mTOR<\/jats:styled-content>\n                    inhibitors to conventional breast cancer therapy has the potential to enhance therapeutic efficacy and\/or overcome innate or acquired resistance. Everolimus, an\n                    <jats:styled-content style=\"fixed-case\">mTOR<\/jats:styled-content>\n                    inhibitor with demonstrated preclinical activity against breast cancer cell lines, has been shown to reverse\n                    <jats:styled-content style=\"fixed-case\">Akt<\/jats:styled-content>\n                    \u2010induced resistance to hormonal therapy and trastuzumab. Phase\n                    <jats:styled-content style=\"fixed-case\">I\u2013II<\/jats:styled-content>\n                    clinical trials have demonstrated that everolimus has promising clinical activity in women with\n                    <jats:styled-content style=\"fixed-case\">HER2<\/jats:styled-content>\n                    \u2010positive,\n                    <jats:styled-content style=\"fixed-case\">HER2<\/jats:styled-content>\n                    \u2010negative, and estrogen receptor\u2013positive breast cancer when combined with\n                    <jats:styled-content style=\"fixed-case\">HER2<\/jats:styled-content>\n                    \u2010targeted therapy, cytotoxic chemotherapy, and hormonal therapy, respectively. Everolimus is generally well tolerated; hematologic abnormalities and stomatitis are most common adverse events when this drug is combined with cytotoxic chemotherapy. Based on these promising results, everolimus is currently under evaluation in a series of phase\n                    <jats:styled-content style=\"fixed-case\">III<\/jats:styled-content>\n                    Breast Cancer Trials of Oral Everolimus (\n                    <jats:styled-content style=\"fixed-case\">BOLERO<\/jats:styled-content>\n                    ) trials of women with\n                    <jats:styled-content style=\"fixed-case\">HER2<\/jats:styled-content>\n                    \u2010positive and estrogen receptor\u2013positive breast cancer. Results of these trials will help to establish the role of everolimus in the treatment of clinically important breast cancer subtypes.\n                  <\/jats:p>","DOI":"10.1002\/j.1875-9114.2012.01084.x","type":"journal-article","created":{"date-parts":[[2012,9,5]],"date-time":"2012-09-05T03:55:15Z","timestamp":1346817315000},"page":"383-396","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Everolimus: Targeted Therapy on the Horizon for the Treatment of Breast Cancer"],"prefix":"10.1002","volume":"32","author":[{"given":"Chad M.","family":"Barnett","sequence":"first","affiliation":[{"name":"Department of Breast Medical Oncology Division of Pharmacy The University of Texas M.D. Anderson Cancer Center Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,3,27]]},"reference":[{"key":"e_1_2_7_2_1","first-page":"1","volume-title":"Cancer facts and figures 2011","author":"American Cancer Society","year":"2011"},{"key":"e_1_2_7_3_1","volume-title":"SEER statistic fact sheet: breast cancer","author":"National Cancer Institute","year":"2012"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.2174\/156800909788166529"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.3816\/CBC.2010.s.016"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1159\/000314280"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1471-4892(03)00071-7"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1362"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10549-010-0986-9"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-06-1609"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.3800296"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-04-0112"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-04-0035"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2713"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.3816\/CBC.2006.n.047"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2007.08.030"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1203973"},{"key":"e_1_2_7_18_1","volume-title":"AFINITOR (everolimus) tablets for oral administration package insert","author":"Novartis Pharmaceuticals Corporation","year":"2011"},{"key":"e_1_2_7_19_1","volume-title":"TORISEL Kit (temsirolimus) injection, for intravenous infusion only package insert","author":"Wyeth Pharmaceuticals Inc","year":"2010"},{"key":"e_1_2_7_20_1","unstructured":"ChowLWC SunY JassemJ et\u00a0al.Phase 3 study of temsirolimus with letrozole or letrozole alone in postmenopausal women with locally advanced or metastatic breast cancer. 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