[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-354213-105":59,"doc-detail-354213-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","dlk1-a-novel-therapeutic-target-in-cancer","DLK1: a novel therapeutic target in cancer","","Delta-like non-canonical Notch ligand 1 (DLK1) is a developmentally restricted, cleavable transmembrane protein that is largely silenced in adult tissues but persists mainly in stem and progenitor compartments of endocrine organs. DLK1 is re-expressed across diverse malignancies, with high prevalence in endocrine and neuroendocrine tumours, where its expression associates with adverse outcomes and a de-differentiated, stem-like phenotype linked to progression and therapeutic resistance. Because DLK1 has cell-surface localization in tumour biology, it is an attractive precision target. The review synthesizes current evidence on DLK1 biology and multiple emerging DLK1-directed strategies.",{"@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":10,"@type":76,"position":81},"https://docshare.wps.com/document/story-novel/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/dlk1-a-novel-therapeutic-target-in-cancer/354213/",{"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/dlk1-a-novel-therapeutic-target-in-cancer/354213.png","ImageObject",300,407,{"name":92,"@type":93},"Pentious","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-29","2026-09-22",true,{"@type":102,"interactionType":103,"userInteractionCount":19},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What is DLK1 and why is it considered a therapeutic target?","Question",{"text":112,"@type":113},"DLK1 is a cleavable transmembrane glycoprotein with tightly regulated expression, re-expressed across many malignancies and localized on the cell surface. Its association with adverse outcomes and stem-like tumour phenotypes makes it attractive for precision targeting.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"Where is DLK1 expressed in normal adult tissues?",{"text":117,"@type":113},"After birth, DLK1 expression is silenced in most healthy tissues and is restricted to stem/progenitor cell populations, especially in endocrine organs such as adrenal cortex and gonads, and in the liver where it marks hepatoblasts.",{"name":119,"@type":110,"acceptedAnswer":120},"What DLK1-directed therapies are described as advancing?",{"text":121,"@type":113},"The review highlights multiple approaches, including afucosylated monoclonal antibodies, antibody–drug conjugates, dendritic cell vaccines, CAR T-cell therapies, and radioimmunotherapy, with early-phase studies reporting encouraging safety and efficacy signals.","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},354213,1792186569,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":8,"category_name":10,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":19,"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},1374404730887,"https://ap-avatar.wpscdn.com/davatar_6f874abed73319feea01a86fa6f0fab8","Endocrine-Related Cancer (2026) 33 e250513  \n[https://doi.org/10.1530/ERC-25-0513](https://doi.org/10.1530/ERC-25-0513)  \nREVIEW  \nReceived 8 December 2025 Accepted 17 April 2026 Available online 22 April 2026  \nVersion of Record published 21 May 2026  \nDLK1: a novel therapeutic target in cancer  \nJames Frederick Henry Pittaway􀀁  \nCentre for Endocrinology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK  \nCorrespondence should be addressed to J F H Pittaway: [j.pittaway@qmul.ac.uk](j.pittaway@qmul.ac.uk)  \nThis paper is part of a special collection highlighting the work of emerging leaders in the endocrine cancer field.  \nGraphical Abstract  \nAbstract  \nDelta-like non-canonical Notch ligand 1 (DLK1) is a cleavable transmembrane protein with tightly regulated, developmentally restricted expression. It is highly expressed during embryogenesis, where it plays a key role in controlling cellular differentiation and proliferation, but is largely silenced in adult tissues, persisting mainly within stem and progenitor compartments of endocrine organs. Notably, DLK1 is consistently re-expressed across a broad range of malignancies, with the highest prevalence observed in endocrine and neuroendocrine tumours, including adrenocortical carcinoma, phaeochromocytoma/paraganglioma, medullary thyroid carcinoma, and neuroblastoma. DLK1 expression is associated with adverse clinical outcomes and is increasingly implicated in maintaining a de-differentiated, stem-like tumour phenotype that might contribute to tumour progression and therapeutic resistance. The restricted expression of DLK1 in normal adult tissues, combined with its cell-surface localisation and functional relevance in tumour biology, makes it an attractive therapeutic target, particularly in endocrine malignancies where targetable options remain limited. Multiple DLK1-directed strategies are now advancing through preclinical and early clinical development,  \nPublished by Bioscientifica Ltd.  \n[https://erc.bioscienti](https://erc.bioscienti)fi[ca.com](ca.com)  \n© 2026 the author(s)  \nThis work is licensed under a Creative Commons Attribution 4 .0 International License.  \nJ F H Pittaway Endocrine-Related Cancer (2026) 33 e250513  \n[https://doi.org/10.1530/ERC-25-0513](https://doi.org/10.1530/ERC-25-0513)  \nincluding afucosylated monoclonal antibodies, antibody–drug conjugates, dendritic cell vaccines, chimeric antigen receptor T-cell therapies, and radioimmunotherapy. Early-phase studies demonstrate encouraging safety profiles and signals of efficacy, with emerging evidence suggesting that tumour-specific factors – such as steroidogenesis, immune microenvironment, and drug efflux mechanisms – may influence response in endocrine cancers. This review collates current evidence on DLK1 biology and therapeutic targeting, with a focus on endocrine and neuroendocrine malignancies. We highlight key novel mechanistic insights, translational challenges, and future opportunities to exploit DLK1 as a precision therapeutic target in these high-need cancer subtypes.  \nKeywords: DLK1; cancer; therapy; treatment; target  \nIntroduction  \nDelta-like non-canonical Notch ligand 1 (DLK1)– previously reported as dlk, fetal antigen 1 (FA1), pre-adipocyte factor 1 (Pref-1), and pG2 – is a single-pass, transmembrane glycoprotein. It consists of six epidermal growth factor (EGF)-like repeats, a transmembrane domain, and a small intracellular tail. In humans, there are two isoforms, one full-length and one membrane-bound, differentiated by the presence of an enzymatic cleavage site at the juxtamembrane region in the former. The active ligand is cleaved from the full-length isoform under the action of TNFα-converting enzyme (TACE) (Fig. 1A) (1, 2).  \nThe DLK1 gene is located on chromosome 14q32 in humans and 12qF1 in mice (3, 4) . It is paternally expressed from the imprinted DLK1-DIO3 gene cluster. Epigenetic regulation at this loc","cbCaigs2oiehEHwO","https://ap.wps.com/l/cbCaigs2oiehEHwO","pdf",431690,11,"English","# Introduction\n## DLK1 structure and isoforms\n## Genomic location and imprinting\n## Adult expression pattern\n# Therapeutic targeting overview\n## DLK1-directed strategies in development","[{\"question\":\"What is DLK1 and why is it considered a therapeutic target?\",\"answer\":\"DLK1 is a cleavable transmembrane glycoprotein with tightly regulated expression, re-expressed across many malignancies and localized on the cell surface. Its association with adverse outcomes and stem-like tumour phenotypes makes it attractive for precision targeting.\"},{\"question\":\"Where is DLK1 expressed in normal adult tissues?\",\"answer\":\"After birth, DLK1 expression is silenced in most healthy tissues and is restricted to stem/progenitor cell populations, especially in endocrine organs such as adrenal cortex and gonads, and in the liver where it marks hepatoblasts.\"},{\"question\":\"What DLK1-directed therapies are described as advancing?\",\"answer\":\"The review highlights multiple approaches, including afucosylated monoclonal antibodies, antibody–drug conjugates, dendritic cell vaccines, CAR T-cell therapies, and radioimmunotherapy, with early-phase studies reporting encouraging safety and efficacy signals.\"}]","DLK1: a novel therapeutic target in cancer | PDF",1790109500,17]