{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:29:13Z","timestamp":1785414553459,"version":"3.56.0"},"reference-count":37,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T00:00:00Z","timestamp":1785110400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Antel Holding Group Ltd."},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["MOP 97917"],"award-info":[{"award-number":["MOP 97917"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"award":["MOP 97917"],"award-info":[{"award-number":["MOP 97917"]}],"id":[{"id":"https:\/\/ror.org\/01gavpb45","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Breast cancer (BC) is the most incidental cancer in women. Patients\u2019 living conditions and survival rates have significantly improved with the success of two first-line endocrine therapies of selective estrogen-receptor modulators (SERMs from 1977) and aromatase inhibitors (AIs from 1995). Unfortunately, both therapies have produced significant resistance. AI resistance reaches 50% in metastatic estrogen-dependent BC cases, leading oncologists to seek a substitute for current therapies. We target the reductive 17\u03b2-hydroxysteroid dehydrogenase type 7 (17\u03b2-HSD7), which stimulates the synthesis of the active estrogen estradiol (E2) and reduces the potent androgen dihydrotestosterone (DHT) simultaneously, triggering negative feedback on 17\u03b2-HSD7 expression. INH7(464), an improved 17\u03b2-HSD7 inhibitor, efficiently blocks estrogen conversion at an IC50 of 92 \u00b1 8 nM. INH7(464) inhibited cell proliferation by decreasing E2 levels and restoring DHT, successively arresting the cell cycle in G0\/G1 phase. In vivo, INH7(464) reduced tumor size by 49% on Day 22 in BC xenografts with T47D. INH7(464) reduced E2 levels in mouse blood circulation and xenograft tumor tissue. There is no demonstrated cytotoxicity or cardiotoxicity of INH7(464) on cellular levels and mouse models under the experimental conditions. 17\u03b2-HSD7 is a potential target for estrogen-dependent BC therapy, while INH7(464) is promising for a preclinical lead compound (PCT\/CA2022\/050966).<\/jats:p>","DOI":"10.3390\/cells15151345","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T11:54:26Z","timestamp":1785153266000},"page":"1345","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Developing Potential Endocrine Therapy Controlling Estradiol and DHT by Targeting 17\u03b2-HSD7 Against ER+ Breast Cancer"],"prefix":"10.3390","volume":"15","author":[{"given":"Ruixuan","family":"Wang","sequence":"first","affiliation":[{"name":"Axe Endocrinology and Nephrology, CHU de Qu\u00e9bec Research Center, Universit\u00e9 Laval, Quebec City, QC G1V 4G2, Canada"},{"name":"Department of Molecular Medicine, Faculty of Medicine, Universit\u00e9 Laval, Quebec City, QC G1V 0A6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqiang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology & Molecular Medicine, Beckman Research Institute, City of Hope, 1500 E. Duarte Rd., Duarte, CA 91010, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5349-3887","authenticated-orcid":false,"given":"Peng","family":"Su","sequence":"additional","affiliation":[{"name":"Axe Endocrinology and Nephrology, CHU de Qu\u00e9bec Research Center, Universit\u00e9 Laval, Quebec City, QC G1V 4G2, Canada"},{"name":"Department of Molecular Medicine, Faculty of Medicine, Universit\u00e9 Laval, Quebec City, QC G1V 0A6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenny","family":"Roy","sequence":"additional","affiliation":[{"name":"Axe Endocrinology and Nephrology, CHU de Qu\u00e9bec Research Center, Universit\u00e9 Laval, Quebec City, QC G1V 4G2, Canada"},{"name":"Department of Molecular Medicine, Faculty of Medicine, Universit\u00e9 Laval, Quebec City, QC G1V 0A6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald","family":"Poirier","sequence":"additional","affiliation":[{"name":"Axe Endocrinology and Nephrology, CHU de Qu\u00e9bec Research Center, Universit\u00e9 Laval, Quebec City, QC G1V 4G2, Canada"},{"name":"Department of Molecular Medicine, Faculty of Medicine, Universit\u00e9 Laval, Quebec City, QC G1V 0A6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9149-375X","authenticated-orcid":false,"given":"Sheng-Xiang","family":"Lin","sequence":"additional","affiliation":[{"name":"Axe Endocrinology and Nephrology, CHU de Qu\u00e9bec Research Center, Universit\u00e9 Laval, Quebec City, QC G1V 4G2, Canada"},{"name":"Department of Molecular Medicine, Faculty of Medicine, Universit\u00e9 Laval, Quebec City, QC G1V 0A6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,27]]},"reference":[{"key":"ref_1","first-page":"229","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. 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