[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-329974-105":59,"doc-detail-329974-en":131},{"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":124,"head_meta":126,"extra_data":128,"updated_unix":130},105,"en","therapeutic-approaches-to-targeting-androgen-receptor-splice-variants-review","Therapeutic Approaches to Targeting Androgen Receptor Splice Variants - Review","","Therapeutic options for advanced prostate cancer have expanded rapidly, with androgen receptor (AR) signaling pathway drugs (androgen receptor targeting agents, ARTAs) remaining central treatments. Prostate cancer driven by AR signaling can shift under treatment pressure to castration-resistant prostate cancer (CRPC), where molecular alterations promote resistant clonal growth. A key resistance mechanism involves AR splice variants (AR-Vs), including constitutively active forms such as AR-V7 that lack the ligand-binding domain. AR-V7 can be measured using validated circulating tumor cell tests to guide effectiveness against AR-V7–positive disease. This review outlines current treatment landscape and evaluates emerging AR-targeted therapeutics under clinical development, categorizing agents by direct or indirect activity against AR-V7.",{"@graph":69,"@context":123},[70,84,106],{"@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/therapeutic-approaches-to-targeting-androgen-receptor-splice-variants-review/329974/",{"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/therapeutic-approaches-to-targeting-androgen-receptor-splice-variants-review/329974.png","ImageObject",300,407,{"name":92,"@type":93},"Jiven","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-29","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",12,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"What are androgen receptor targeting agents (ARTAs) and why are they important in advanced prostate cancer?","Question",{"text":113,"@type":114},"ARTAs target the androgen receptor (AR) signaling pathway and represent the mainstream treatment approach that can control disease for extended periods. Their effectiveness is influenced by how cancer adapts under treatment pressure.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"How do AR splice variants contribute to castration-resistant prostate cancer (CRPC)?",{"text":118,"@type":114},"AR splice variants (AR-Vs) are truncated AR isoforms that can be constitutively active without androgen ligands. This provides a resistance mechanism that supports continued AR signaling despite conventional anti-androgen therapy.",{"name":120,"@type":111,"acceptedAnswer":121},"Why is AR-V7 clinically significant, and how can it be measured?",{"text":122,"@type":114},"AR-V7 is the most extensively studied splice variant because it activates AR signaling without the ligand-binding domain. It may be measured noninvasively using validated circulating tumor cell (CTC) tests.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},329974,1790116686,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":140,"language":141,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":67,"update_tm":145,"read_time":146},1099513958607,"https://ap-avatar.wpscdn.com/avatar/100002390cf8733938c?x-image-process=image/resize,m_fixed,w_180,h_180&k=1778829742770036399","cells  \nReview  \nTherapeutic Approaches to Targeting Androgen Receptor Splice Variants  \nViolet A. Daniels 1, Jun Luo 1,2, Channing J. Paller 2, * and Mayuko Kanayama 1, *  \nCitation: Daniels, V.A.; Luo, J.; Paller, C.J.; Kanayama, M. Therapeutic Approaches to Targeting Androgen Receptor Splice Variants. Cells 2024, 13, 104. [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)cells13010104  \nAcademic Editor: Hiroshi Miyamoto  \nReceived: 5 December 2023  \nRevised: 31 December 2023  \nAccepted: 1 January 2024  \nPublished: 4 January 2024  \nCopyright: © 2024 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 ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \n1 Department of Urology, James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; [vdaniel5@jhmi.edu](vdaniel5@jhmi.edu) (V.A.D.); [jluo2@jhmi.edu](jluo2@jhmi.edu) (J.L.)  \n2 Departments of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA  \n* Correspondence: [cpaller1@jhmi.edu](cpaller1@jhmi.edu) (C.J.P.); [mkanaya1@jhmi.edu](mkanaya1@jhmi.edu) (M.K.); Tel.: +1-202-660-6500 (C.J.P.);+1-443-333-3997 (M.K.)  \nAbstract: Therapeutic options for advanced prostate cancer have vastly expanded over the last decade and will continue to expand in the future. Drugs targeting the androgen receptor (AR) signaling pathway, i.e., androgen receptor targeting agents (ARTAs), remain the mainstream treatments that are increasingly transforming the disease into one that can be controlled for an extended period of time. Prostate cancer is inherently addicted to AR. Under the treatment pressure of ARTA, molecular alterations occur, leading to the clonal expansion of resistant cells in a disease state broadly categorized as castration-resistant prostate cancer (CRPC) . One castration resistance mechanism involves AR splice variants (AR-Vs) lacking the ligand-binding domain. Some AR-Vs have been identified as constitutively active, capable of activating AR signaling pathways without androgenic ligands. Among these variants, AR-V7 is the most extensively studied and may be measured noninvasively using validated circulating tumor cell (CTC) tests. In the context of the evolving prostate cancer treatment landscape, novel agents are developed and evaluated for their efficacy in targeting AR-V7 . In patients with metastatic CRPC (mCRPC), the availability of the AR-V7 tests will make it possible to determine whether the treatments are effective for CTC AR-V7-positive disease, eventhough the treatments may not be specifically designed to target AR-V7 . In this review, we will first outline the current prostate cancer treatment landscape, followed by an in-depth review of relatively newer prostate cancer therapeutics, focusing on AR-targeting agents under clinical development. These drugs are categorized from the standpoint of their activities against AR-V7 through direct or indirect mechanisms.  \nKeywords: androgen receptor splice variants; AR-V7; castration-resistant prostate cancer  \n1. Introduction  \nProstate cancer is the second-leading cause of cancer-related deaths among men in the United States [1] . This warrants a large body of research to decipher the intricate biology of the disease and devise effective treatments. The hallmark of prostate cancer progression is the androgen receptor (AR) signaling pathway, which is mainly responsible for prostate cell survival, proliferation, and resistance to treatment. Despite significant advancements in the targeting of this pathway, the emergence of castration-resistant prostate cancer (CRPC) and its inherent resistance to conventional anti-androgen therapies have und","cbCainc20kAW1XRb","https://ap.wps.com/l/cbCainc20kAW1XRb","pdf",1866026,17,"English","# Introduction\n## Androgen receptor signaling and castration-resistant prostate cancer\n## AR splice variants and the role of AR-V7\n## Therapeutic implications and circulating tumor cell testing","[{\"question\":\"What are androgen receptor targeting agents (ARTAs) and why are they important in advanced prostate cancer?\",\"answer\":\"ARTAs target the androgen receptor (AR) signaling pathway and represent the mainstream treatment approach that can control disease for extended periods. Their effectiveness is influenced by how cancer adapts under treatment pressure.\"},{\"question\":\"How do AR splice variants contribute to castration-resistant prostate cancer (CRPC)?\",\"answer\":\"AR splice variants (AR-Vs) are truncated AR isoforms that can be constitutively active without androgen ligands. This provides a resistance mechanism that supports continued AR signaling despite conventional anti-androgen therapy.\"},{\"question\":\"Why is AR-V7 clinically significant, and how can it be measured?\",\"answer\":\"AR-V7 is the most extensively studied splice variant because it activates AR signaling without the ligand-binding domain. It may be measured noninvasively using validated circulating tumor cell (CTC) tests.\"}]","Therapeutic Approaches to Targeting Androgen Receptor Splice Variants - Review | PDF",1789986397,43]