{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,8]],"date-time":"2026-11-08T19:22:47Z","timestamp":1794165767136,"version":"4.8.0"},"reference-count":78,"publisher":"American Society for Clinical Investigation","issue":"21","license":[{"start":{"date-parts":[[2026,11,9]],"date-time":"2026-11-09T00:00:00Z","timestamp":1794182400000},"content-version":"vor","delay-in-days":41,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Breast Cancer Research Foundation","award":["BCRF-24-003"],"award-info":[{"award-number":["BCRF-24-003"]}],"id":[{"id":"https:\/\/ror.org\/0348ff195","id-type":"ROR","asserted-by":"crossref"}]},{"name":"DOD Peer Reviewed Cancer Research Program","award":["BC073237"],"award-info":[{"award-number":["BC073237"]}]},{"name":"National Cancer Institute","award":["CA125123"],"award-info":[{"award-number":["CA125123"]}]},{"name":"National Cancer Institute","award":["P01CA166009"],"award-info":[{"award-number":["P01CA166009"]}]},{"name":"Swim Across America","award":["Swim Across America Cancer Research Grant"],"award-info":[{"award-number":["Swim Across America Cancer Research Grant"]}],"id":[{"id":"https:\/\/ror.org\/05d8ft347","id-type":"ROR","asserted-by":"crossref"}]},{"name":"N\/A","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,11,9]]},"abstract":"<jats:p>\n                    Resistance to endocrine therapy (ET) in estrogen receptor\u2013positive (ER\n                    <jats:sup>+<\/jats:sup>\n                    ) breast cancer is mediated by Notch signaling, but the clinical application of anti-Notch therapy has been limited by the lack of predictive biomarkers. To identify Notch-regulated biomarkers, we conducted a presurgical window study evaluating ET combined with the \u03b3-secretase inhibitor (GSI) MK-0752. RNA expression in tumors was measured using an Affymetrix array and by real-time PCR (RT-PCR). ET plus GSI showed more genes were decreased than ET alone. Specifically,\n                    <jats:italic>DAXX<\/jats:italic>\n                    ,\n                    <jats:italic>NOXA<\/jats:italic>\n                    , and\n                    <jats:italic>LFNG<\/jats:italic>\n                    RNAs were increased, while 15 additional transcripts were decreased. Mechanistically, GSI reduced Notch1 occupancy at CSL-binding elements within\n                    <jats:italic>HES1<\/jats:italic>\n                    ,\n                    <jats:italic>HEY2<\/jats:italic>\n                    ,\n                    <jats:italic>HEYL<\/jats:italic>\n                    ,\n                    <jats:italic>CCND1<\/jats:italic>\n                    ,\n                    <jats:italic>MKI67<\/jats:italic>\n                    , and\n                    <jats:italic>DAXX<\/jats:italic>\n                    genes, and inhibited cancer stem cells (CSCs) by 90%\u2013100%. This anti-CSC effect required DAXX, while GSI treatment or Notch1\/4 knockdown increased DAXX expression, suggesting transcriptional repression by Notch. Using mouse tumor xenograft studies, ET plus MK-0752 resulted in complete regression of MCF-7 tumors, with DAXX-high tumors showing greater treatment sensitivity. Clinically, high DAXX expression was associated with improved recurrence-free and overall survival. This study found that anti-Notch plus ET in ER\n                    <jats:sup>+<\/jats:sup>\n                    breast cancer inhibits CSCs by increasing DAXX, a promising predictive biomarker. These findings support clinical evaluation of therapies that increase DAXX expression.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.172506","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T16:17:04Z","timestamp":1790698624000},"source":"Crossref","is-referenced-by-count":0,"title":["Anti-Notch plus endocrine therapy in ER+ breast cancer inhibits cancer stem cells by increasing DAXX"],"prefix":"10.1172","volume":"11","author":[{"given":"Kathy S.","family":"Albain","sequence":"first","affiliation":[{"name":"Department of Medicine, Division of Hematology\/Oncology, Loyola University Chicago Stritch School of Medicine, Cardinal Bernardin Cancer Center, Maywood, Illinois, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debra","family":"Wyatt","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology, Loyola University Chicago, Maywood, Illinois, 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