[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-357980-105":59,"doc-detail-357980-en":130},{"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":123,"head_meta":125,"extra_data":127,"updated_unix":129},105,"en","dll3-targeted-strategies-in-advanced-prostate-cancer-current-evidence-and-future-perspectives","DLL3-Targeted Strategies in Advanced Prostate Cancer - Current Evidence and Future Perspectives","","Androgen receptor (AR) signaling is central to systemic treatment of advanced prostate cancer, yet aggressive subtypes can arise de novo with neuroendocrine features or emerge under therapy via lineage plasticity and AR independence. These phenotypes fall within aggressive-variant prostate cancer (AVPC), including histologically confirmed NEPC (de novo and treatment-emergent) and AVPC defined clinically or molecularly. Rapid progression, visceral dissemination, discordant low PSA, and poor prognosis characterize these states, while current NEPC/AVPC therapies—mostly platinum chemotherapy—offer limited, transient benefit. DLL3, a tumor-associated Notch ligand aberrantly upregulated in neuroendocrine malignancies, is enriched in neuroendocrine prostate cancer and represents a biomarker and actionable target. This review evaluates biological rationale, translational evidence, and emerging clinical data for DLL3-targeted therapies, including antibody-drug conjugates, T-cell engagers, and DLL3-directed radiopharmaceuticals, emphasizing the need for biomarker-guided patient selection and optimized trial design.",{"@graph":69,"@context":122},[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/dll3-targeted-strategies-in-advanced-prostate-cancer-current-evidence-and-future-perspectives/357980/",{"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/dll3-targeted-strategies-in-advanced-prostate-cancer-current-evidence-and-future-perspectives/357980.png","ImageObject",300,407,{"name":92,"@type":93},"LangkahRina","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-01","2026-09-23",true,{"@type":102,"interactionType":103,"userInteractionCount":34},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What does the review identify as a defining feature of aggressive-variant prostate cancer (AVPC)?","Question",{"text":112,"@type":113},"AVPC includes aggressive states driven by lineage plasticity and androgen receptor independence, leading to rapid progression, visceral dissemination, and poor prognosis with limited effective therapies.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How is DLL3 connected to neuroendocrine prostate cancer in the document?",{"text":117,"@type":113},"The review states that DLL3 expression is enriched in neuroendocrine tumor cells, detected in about 76.6% of castration-resistant NEPC compared with 12.5% in castration-resistant adenocarcinoma.",{"name":119,"@type":110,"acceptedAnswer":120},"Which DLL3-targeted treatment approaches are discussed, and what determines clinical utility?",{"text":121,"@type":113},"The document summarizes antibody-drug conjugates, T-cell engagers, and DLL3-directed radiopharmaceuticals. Their usefulness is described as depending on improved biomarker-based patient selection and prostate-specific trial design.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},357980,1790519565,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":34,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145},962090893776,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","Drugs (2026) 86:1489–1511  \n[https://doi.org/10.1007/s40265-026-02355-5](https://doi.org/10.1007/s40265-026-02355-5)  \nDLL3‑Targeted Strategies in Advanced Prostate Cancer: Current Evidence and Future Perspectives  \nGiovanna Pecoraro1,2,3 · Alberto De Giorgi1,4 · Giulia Montelatici1,5 · Giuseppe Salfi1 · Hui‑Ming Lin1 · Fabio Turco1 · TarekTaha6,7 · Himisha Beltran8 · Johann de Bono6,7,9 · Rahul Raj Aggarwal10 · Gunhild von Amsberg11 · Markus Joerger12 · Martina Imbimbo1 · Ilaria Colombo1 · Silke Gillessen1,13 · Martino Pedrani1  \nReceived: 16 April 2026 / Accepted: 3 June 2026 / Published online: 29 July 2026 © The Author(s) 2026  \nAbstract  \nInhibition of androgen receptor (AR) signaling remains the cornerstone of systemic therapy for advanced prostate cancer (PC). However, a subset of aggressive tumors either arises de novo with neuroendocrine features or emerges under treatment pressure through lineage plasticity and AR independence. These lethal states are encompassed within the spectrum of aggressive-variant prostate cancer (AVPC), an umbrella term that includes both histologically confirmed neuroendocrine prostate cancer (NEPC)—comprising de novo NEPC and treatment-emergent NEPC (t-NEPC)—and clinically or molecularly defined AVPC lacking histologic confirmation but sharing neuroendocrine-like, AR-indifferent, or small-cell features. These phenotypes are characterized by rapid progression, visceral dissemination, low or discordant prostate-specific antigen (PSA) levels relative to tumor burden, and poor prognosis. Treatment options for NEPC/AVPC remain limited and largely rely on platinum-based chemotherapy, which usually provides only modest and transient benefit. This unmet need has intensified interest in lineage-associated vulnerabilities. Delta-like ligand 3 (DLL3), an inhibitory Notch ligand with restricted expression in normal adult tissues, is aberrantly upregulated in several neuroendocrine malignancies and has emerged as a clinically actionable target. In prostate cancer, DLL3 expression is enriched in neuroendocrine tumor cells, being detected in approximately 76.6% of castration-resistant NEPC compared with only 12.5% of castration-resistant adenocarcinoma, supporting its development as both a biomarker and therapeutic vulnerability. Clinical success of DLL3-targeted therapies in small-cell lung cancer further supports evaluation of DLL3-directed strategies in NEPC and related AVPC states. This review summarizes the biological rationale, translational evidence, and emerging clinical data supporting DLL3-targeted therapies in prostate cancer. Investigational platforms include antibody-drug conjugates, bispecific and trispecific T-cell engagers, and DLL3-directed radiopharmaceuticals. Early clinical studies suggest that activity is largely confined to DLL3-expressing neuroendocrine tumors, highlighting the importance of biomarker-guided patient selection. Delta-like ligand 3-directed therapies may reshape the management of DLL3-expressing prostate cancer if ongoing efforts to refine biomarkers improve patient enrichment and optimize trial design are successfully translated into clinical practice.  \n* Martino Pedrani [martino.pedrani@eoc.ch](martino.pedrani@eoc.ch)  \nGunhild von Amsberg  \n[g.von-amsberg@uke.de](g.von-amsberg@uke.de)  \n1 Oncology Institute of Southern Switzerland (IOSI), Ente Ospedaliero Cantonale (EOC), Bellinzona, Switzerland  \n2 Institute of Oncology Research (IOR), Bellinzona, Switzerland  \n3 Clinical and Translational Oncology, Scuola Superiore Meridionale, Via Mezzocannone 4, 80134 Naples, Italy  \n4 Medical Oncology Department, Turin University, Turin, Italy  \n5 Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy  \n6 The Institute of Cancer Research, London, UK  \n7 The Royal Marsden NHS Foundation Trust, London, UK  \n8 Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA  \n9 Division of Clinical Studies, ","cbCaipX5FIrO4KTU","https://ap.wps.com/l/cbCaipX5FIrO4KTU","pdf",1605428,23,"English","# Abstract\n# Key Points\n# 1 Introduction","[{\"question\":\"What does the review identify as a defining feature of aggressive-variant prostate cancer (AVPC)?\",\"answer\":\"AVPC includes aggressive states driven by lineage plasticity and androgen receptor independence, leading to rapid progression, visceral dissemination, and poor prognosis with limited effective therapies.\"},{\"question\":\"How is DLL3 connected to neuroendocrine prostate cancer in the document?\",\"answer\":\"The review states that DLL3 expression is enriched in neuroendocrine tumor cells, detected in about 76.6% of castration-resistant NEPC compared with 12.5% in castration-resistant adenocarcinoma.\"},{\"question\":\"Which DLL3-targeted treatment approaches are discussed, and what determines clinical utility?\",\"answer\":\"The document summarizes antibody-drug conjugates, T-cell engagers, and DLL3-directed radiopharmaceuticals. Their usefulness is described as depending on improved biomarker-based patient selection and prostate-specific trial design.\"}]","DLL3-Targeted Strategies in Advanced Prostate Cancer - Current Evidence and Future Perspectives | PDF",1790132425,58]