[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-358844-105":59,"doc-detail-358844-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","notch-signaling-in-the-tumor-microenvironment-recent-advances-and-targeted-therapeutics","Notch signaling in the tumor microenvironment - recent advances and targeted therapeutics","","The Notch signaling pathway is an evolutionarily conserved mechanism that governs cell-cell communication and exerts multifaceted control over the tumor microenvironment (TME). This review synthesizes canonical and non-canonical signaling cascades, and explains Notch’s dual behavior in tumorigenesis as either oncogenic or tumor-suppressive. It details how Notch signaling regulates major TME components, including immune cell differentiation and function, angiogenesis, cancer-associated fibroblasts, and cancer stem cell maintenance, and summarizes Notch-targeting therapeutics to support clinical translation and antitumor immunity.",{"@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/notch-signaling-in-the-tumor-microenvironment-recent-advances-and-targeted-therapeutics/358844/",{"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/notch-signaling-in-the-tumor-microenvironment-recent-advances-and-targeted-therapeutics/358844.png","ImageObject",300,407,{"name":92,"@type":93},"Miles","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-29","2026-09-23",true,{"@type":102,"interactionType":103,"userInteractionCount":52},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What is the main focus of the review on Notch signaling in the TME?","Question",{"text":112,"@type":113},"The review provides an overview of core Notch pathway components and both canonical and non-canonical signaling mechanisms, emphasizing how Notch shapes the tumor microenvironment.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How does Notch signaling influence tumorigenesis according to the review?",{"text":117,"@type":113},"Notch signaling can function as either an oncogene or a tumor suppressor, depending on context, and it modulates key cellular constituents within the TME.",{"name":119,"@type":110,"acceptedAnswer":120},"Which therapeutic strategies targeting Notch signaling are highlighted?",{"text":121,"@type":113},"The review highlights γ-secretase inhibitors and modulators, monoclonal antibodies against ligands and receptors, small-molecule inhibitors, and combination approaches integrating immune checkpoint inhibitors, CAR immune cell therapy, cancer vaccines, and oncolytic viruses.","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},358844,1790623088,{"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":52,"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},13056703019404,"https://ap-avatar.wpscdn.com/davatar_29158cc5080c5b710cf443261637dec0","Chen et al. Molecular Cancer (2026) 25:50 Molecular Cancer  \n[https://doi.org/10.1186/s12943-025-02555-9](https://doi.org/10.1186/s12943-025-02555-9)  \nREVIEW Open Access  \nNotch signaling in the tumor microenvironment: recent advancesand targeted therapeutics  \nDi Chen1†, Xinyu Gu2†, Jingdian Liu1†, Lixia Xu3†, Zi Ye4, Peng Gao1, Hongjiang Li1, Henan Jiao1, Peidong Liu 1, Guihong Li1, Yazhou Miao1, Changhe Pang1, Bin Yu1, Beibei Nie1, Jing Yan5, Dongming Yan1, Xuqiang Zhu1,7*, Yuting He6,7*, Shen Shen3,7* and Xueyuan Li 1,7*  \nAbstract  \nThe Notch signaling pathway, an evolutionarily conserved mechanism governing cell-cell communication, plays a pivotal and multifaceted role in shaping the tumor microenvironment (TME) . This review provides a comprehensive overview of the core components and signaling mechanisms of the Notch pathway, encompassing both canonical and non-canonical signaling cascades. It further examines the dual functionality of Notch in tumorigenesis, functioning as either an oncogene or a tumor suppressor. A central focus of this review is the detailed investigation of the molecular mechanisms through which Notch signaling modulates key cellular constituents of the TME. Recent advances are systematically summarized, with emphasis on the role of Notch in regulating immune cell differentiation and function, angiogenesis, modulating cancer-associated fibroblasts, and maintenance of cancer stem cells. To facilitate clinical translation, the review highlights emerging therapeutic strategies targeting the Notch pathway, including γ-secretase inhibitors and modulators, monoclonal antibodies against ligands and receptors, small molecule inhibitors, and combination therapies integrating immune checkpoint inhibitors, chimeric antigen receptor immune cell therapy, cancer vaccines, and oncolytic viruses. Collectively, this work offers a systematic synthesis of recent progress in understanding the diverse roles of Notch signaling within the TME, emphasizing the therapeutic potential of modulating Notch signaling to reprogram the TME and enhance antitumor immunity.  \nKeywords Notch signaling, Tumor microenvironment, Immune cells, Cancer-associated fibroblasts, Immunotherapy  \n†Di Chen, Xinyu Gu, Jingdian Liu and Lixia Xu contributed equally to this work.  \n*Correspondence:  \nXuqiang Zhu [zhuxuqiang2007@163.com](zhuxuqiang2007@163.com)[ ](zhuxuqiang2007@163.com)Yuting He [fccheyt1@zzu.edu.cn](fccheyt1@zzu.edu.cn)[ ](fccheyt1@zzu.edu.cn)Shen Shen [shenshenay@163.com](shenshenay@163.com)[ ](shenshenay@163.com)Xueyuan Li[lixueyuan-82@163.com](lixueyuan-82@163.com)  \n1Department of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, China  \n2Henan Key Laboratory of Cancer Epigenetics, Cancer Institute, The First Affiliated Hospital, College of Clinical Medicine, Henan University of Science and Technology, Luoyang, Henan, China  \n3Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, China 4Department of Scientific Research, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, China 5Department of MRI, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, China  \n6Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China  \n7The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Erqi District, Zhengzhou 450052, Henan, China  \n© The Author(s) 2026. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you m","cbCaiux2VgbtzMnT","https://ap.wps.com/l/cbCaiux2VgbtzMnT","pdf",3266229,29,"English","# Abstract\n# Introduction","[{\"question\":\"What is the main focus of the review on Notch signaling in the TME?\",\"answer\":\"The review provides an overview of core Notch pathway components and both canonical and non-canonical signaling mechanisms, emphasizing how Notch shapes the tumor microenvironment.\"},{\"question\":\"How does Notch signaling influence tumorigenesis according to the review?\",\"answer\":\"Notch signaling can function as either an oncogene or a tumor suppressor, depending on context, and it modulates key cellular constituents within the TME.\"},{\"question\":\"Which therapeutic strategies targeting Notch signaling are highlighted?\",\"answer\":\"The review highlights γ-secretase inhibitors and modulators, monoclonal antibodies against ligands and receptors, small-molecule inhibitors, and combination approaches integrating immune checkpoint inhibitors, CAR immune cell therapy, cancer vaccines, and oncolytic viruses.\"}]","Notch signaling in the tumor microenvironment - recent advances and targeted therapeutics | PDF",1790135448,73]