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However, endoxifen\u2019s antitumor effects may be related to additional molecular mechanisms of action, apart from its effects on ER. In phase 1\/2 clinical studies, the efficacy of Z-endoxifen, the active isomer of endoxifen, was evaluated in patients with endocrine-refractory metastatic breast cancer as well as in patients with gynecologic, desmoid, and hormone-receptor positive solid tumors, and demonstrated substantial oral bioavailability and promising antitumor activity. Apart from its potent anticancer effects, Z-endoxifen appears to result in similar or even greater bone agonistic effects while resulting in little or no endometrial proliferative effects compared with tamoxifen. In this review, we summarize the preclinical and clinical studies evaluating endoxifen in the context of breast and other solid tumors, the potential benefits of endoxifen in bone, as well as its emerging role as an antimanic agent in bipolar disorder. In total, the summarized body of literature provides compelling arguments for the ongoing development of Z-endoxifen as a novel drug for multiple indications.<\/jats:p>","DOI":"10.1210\/endocr\/bqab191","type":"journal-article","created":{"date-parts":[[2021,9,4]],"date-time":"2021-09-04T13:40:55Z","timestamp":1630762855000},"source":"Crossref","is-referenced-by-count":31,"title":["Endoxifen, an Estrogen Receptor Targeted Therapy: From Bench to Bedside"],"prefix":"10.1210","volume":"162","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5451-0052","authenticated-orcid":false,"given":"Swaathi","family":"Jayaraman","sequence":"first","affiliation":[{"name":"Department of Oncology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2872-3123","authenticated-orcid":false,"given":"Joel M","family":"Reid","sequence":"additional","affiliation":[{"name":"Department of Oncology, Mayo Clinic, Rochester, MN 55905, USA"},{"name":"Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3406-470X","authenticated-orcid":false,"given":"John R","family":"Hawse","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4383-270X","authenticated-orcid":false,"given":"Matthew P","family":"Goetz","sequence":"additional","affiliation":[{"name":"Department of Oncology, Mayo Clinic, Rochester, MN 55905, USA"},{"name":"Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2021,9,4]]},"reference":[{"issue":"1","key":"2022012509004833700_CIT0001","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21654","article-title":"Cancer statistics, 2021","volume":"71","author":"Siegel","year":"2021","journal-title":"CA Cancer J Clin."},{"key":"2022012509004833700_CIT0002","doi-asserted-by":"crossref","first-page":"620","DOI":"10.3389\/fphar.2017.00620","article-title":"Tamoxifen from failed contraceptive pill to best-selling breast cancer medicine: a case-study in pharmaceutical innovation","volume":"8","author":"Quirke","year":"2017","journal-title":"Front Pharmacol."},{"issue":"2","key":"2022012509004833700_CIT0003","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1038\/bjc.1971.33","article-title":"A new anti-oestrogenic agent in late breast cancer. 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