[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-353355-105":59,"doc-detail-353355-en":122},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":115,"head_meta":117,"extra_data":119,"updated_unix":121},105,"en","estrogen-receptors-and-enzymes-involved-in-estrogen-synthesis-as-breast-cancer-treatment-targets","Estrogen Receptors and Enzymes Involved in Estrogen Synthesis as Breast Cancer Treatment Targets","","Estrogens, especially 17β-estradiol (E2), drive initiation and progression of breast cancer, so therapies focus on blocking estrogen receptors or suppressing estrogen formation via key pathway enzymes. Selective estrogen receptor modulators (SERMs) can be effective, yet resistance frequently develops and triple-negative breast cancer remains unresponsive due to absent ERα. Aromatase, steroid sulfatase, and 17β-hydroxysteroid dehydrogenases are highlighted as drug targets, with aromatase inhibitors already used clinically. The review summarizes recent ER and enzyme modulators/inhibitors and outlines directions for further development.",{"@graph":69,"@context":114},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/estrogen-receptors-and-enzymes-involved-in-estrogen-synthesis-as-breast-cancer-treatment-targets/353355/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/estrogen-receptors-and-enzymes-involved-in-estrogen-synthesis-as-breast-cancer-treatment-targets/353355.png","ImageObject",300,407,{"name":92,"@type":93},"RuangKosong","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-29","2026-09-22",true,{"@type":102,"interactionType":103,"userInteractionCount":52},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108],{"name":109,"@type":110,"acceptedAnswer":111},"Which enzymes in the estrogen synthesis pathway are emphasized as drug targets?","Question",{"text":112,"@type":113},"The review focuses on aromatase, steroid sulfatase (sulfatase), and 17β-hydroxysteroid dehydrogenases (HSD17B), noting that aromatase inhibitors are already clinically used while other inhibitors remain under investigation.","Answer","https://schema.org",{"og:url":83,"og:type":116,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":118,"canonical":83},"index,follow",{"doc_id":120,"site_id":62},353355,1790179156,{"code":4,"msg":5,"data":123},{"doc_id":120,"user_id":124,"nickname":92,"user_avatar":125,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":126,"file_id":127,"file_url":128,"file_type":129,"file_size":130,"view_count":52,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":56,"language":131,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":132,"faqs":133,"seo_title":134,"seo_description":67,"update_tm":135,"read_time":136},962090883219,"https://ap-avatar.wpscdn.com/davatar_276721f389ce27ea32af1340a28f341c","Review  \nEstrogen Receptors and Enzymes Involved in Estrogen Synthesis as Breast Cancer Treatment Targets  \nBarbara Licznerska, Hanna Szaefer , Hanna Sobierajska  and Wanda Baer-Dubowska *  \nAcademic Editors: Matin Sheriff and Kazuhiko Kuwahara  \nReceived: 18 May 2026  \nRevised: 16 July 2026  \nAccepted: 29 July 2026  \nPublished: 30 July 2026  \nCopyright: © 2026 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license.  \nPoznan University of Medical Sciences, Department of Pharmaceutical Biochemistry, 60-806 Pozna ´n, Poland;  \n[barlicz@ump.edu.pl](barlicz@ump.edu.pl) (B.L.); [hszaefer@ump.edu.pl](hszaefer@ump.edu.pl) (H.S.); [bernatha@ump.edu.pl](bernatha@ump.edu.pl) (H.S.)  \n* [Correspondence: baerw@ump.edu.pl](Correspondence: baerw@ump.edu.pl)  \nAbstract  \nEstrogens, particularly the most active 17β-estradiol (E2), play a crucial role in the initiation and development of breast cancer. Therefore, current treatment strategies are based on interfering with estrogen receptors (ERs) via pure antiestrogens or selective modulators (SERMs) or by inhibiting estrogen synthesis through key enzymes in this pathway. While SERMs are generally effective, resistance often develops. Moreover, they cannot be used to treat triple-negative breast cancers (TNBCs) . Three critical enzymes in the estrogen synthesis pathway, namely aromatase, sulfatase, and 17β-hydroxysteroid dehydrogenases, are of particular interest as drug targets. Some, such as aromatase inhibitors, are already used in clinical practice, while the other two remain under intensive investigation. Several comprehensive reviews have been published on ER modulators or individual enzyme inhibitors. This paper attempts to summarize recent data on modulators/inhibitors of both the ER and the major enzymes involved in estrogen biosynthesis and offers a perspective on their further development.  \nKeywords: breast cancer; estrogen receptors; aromatase; steroid sulfatase; 17β-hydroxysteroid dehydrogenases  \n1. Introduction  \nApproximately 70% of breast cancers are estrogen-dependent. Therefore, targeting either the action or the formation of estrogens is the major approach to treat these cancers. To block the action of estrogens, several estrogen receptor (ER) inhibitors, mainly ERα, have been developed, including pure antiestrogens and selective estrogen receptor modulators (SERMs) . While the latter are generally effective for both breast cancer treatment and prophylaxis, some patients develop resistance [1] . Several factors may contribute to this process, and breast tumor heterogeneity and microenvironment are probably the most important [2] .  \nMoreover, triple-negative breast cancer (TNBC), which accounts for approximately 15% of total breast cancer cases, does not respond to ER modulators due to the absence of ERα. Possible targets for improving TNBC include estrogen signaling through membranous ERα-36, which could reactivate silenced ERα. Inhibition of enzymes involved in estrogen synthesis might be applicable, probably not only to the treatment of ERα+ breast cancer.  \nLike other primates, humans can synthesize sex steroid hormones independently of gonadal sources by secreting dehydroepiandrosterone (DHEA) and its sulfated derivative, dehydroepiandrosterone sulfate (DHEA-S), which are then locally metabolized into active hormones [3] . Therefore, in postmenopausal women, sex steroids, including estrogens, are  \npredominantly produced in extragonadal tissues from adrenal precursors, a system termed“intracrinology” [4] . Three enzymes are particularly important in estrogen synthesis from DHEA and DHEA-S, both in gonadal and intracrine contexts: aromatase (CYP19), steroidsulfatase (STS), and 17β-hydroxysteroid dehydrogenases (HSD17B). Beyond their primary activities, these enzymes contribute to the inactivation of steroid receptor ligands, facilitating cont","cbCaipaZ8RbvhMS1","https://ap.wps.com/l/cbCaipaZ8RbvhMS1","pdf",2319042,"English","# Abstract\n# Introduction\n# Estrogen Receptors and Their Modulation\n## Estrogen Receptors and Signaling Mechanisms","[{\"question\":\"Which enzymes in the estrogen synthesis pathway are emphasized as drug targets?\",\"answer\":\"The review focuses on aromatase, steroid sulfatase (sulfatase), and 17β-hydroxysteroid dehydrogenases (HSD17B), noting that aromatase inhibitors are already clinically used while other inhibitors remain under investigation.\"}]","Estrogen Receptors and Enzymes Involved in Estrogen Synthesis as Breast Cancer Treatment Targets | PDF",1790104856,48]