{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T01:06:00Z","timestamp":1791162360375,"version":"4.1.0"},"reference-count":38,"publisher":"Portland Press Ltd.","issue":"1","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2009,1,1]]},"abstract":"<jats:p>Tamoxifen is the most commonly used drug to treat breast cancer and acts by blocking ER\u03b1 (oestrogen receptor \u03b1) signalling. Although highly effective, its usefulness is limited by the development of resistance. Given this, strategies that limit resistance by sensitizing cells to tamoxifen may be of use in the clinic. To gain insight into how this might be achieved, we used chemical and genetic screens to identify targets and small-molecule inhibitors that cause tamoxifen sensitization. A high-throughput genetic screen, using an RNA interference library targeting 779 kinases and related proteins, identified the PDK1 (phosphoinositide-dependent kinase 1) signalling pathway as a strong determinant of sensitivity to multiple ER\u03b1 antagonists, including tamoxifen. A chemical screen using existing drugs and known kinase inhibitors also identified inhibitors of the PDK1 pathway, including triciribine and tetrandrine. Aside from identifying novel agents and targets for tamoxifen sensitization, this approach also provides evidence that performing chemical and genetic screens in parallel may be useful.<\/jats:p>","DOI":"10.1042\/bj20081682","type":"journal-article","created":{"date-parts":[[2008,11,4]],"date-time":"2008-11-04T09:38:31Z","timestamp":1225791511000},"page":"361-371","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":54,"title":["Parallel RNAi and compound screens identify the PDK1 pathway as a target for tamoxifen sensitization"],"prefix":"10.1042","volume":"417","author":[{"given":"Elizabeth","family":"Iorns","sequence":"first","affiliation":[{"name":"The Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, Fulham Road, London SW3 6JB, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher\u00a0J.","family":"Lord","sequence":"additional","affiliation":[{"name":"The Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, Fulham Road, London SW3 6JB, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan","family":"Ashworth","sequence":"additional","affiliation":[{"name":"The Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, Fulham Road, London SW3 6JB, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2008,12,12]]},"reference":[{"key":"2021112214342475000_B1","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.1016\/S0140-6736(97)11423-4","article-title":"Tamoxifen for early breast cancer: an overview of the randomised trials. 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