[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-367452-105":59,"doc-detail-367452-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","the-molecular-mechanism-and-therapeutic-landscape-of-copper-and-cuproptosis-in-cancer","The molecular mechanism and therapeutic landscape of copper and cuproptosis in cancer","","Copper, an essential micronutrient, is tightly regulated in cells and the body, and disruptions in copper homeostasis are linked to multiple cancers. Imbalances can contribute to tumor progression and therapeutic resistance, while manipulating copper levels offers therapeutic potential. This review explains copper homeostasis at cellular and systemic levels, details cuproptosis milestones and mechanisms in mitochondria-dependent and independent pathways, and summarizes roles in cancer and immune interactions, therapeutic opportunities, gene associations, biomarkers, and remaining challenges.",{"@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/the-molecular-mechanism-and-therapeutic-landscape-of-copper-and-cuproptosis-in-cancer/367452/",{"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/the-molecular-mechanism-and-therapeutic-landscape-of-copper-and-cuproptosis-in-cancer/367452.png","ImageObject",300,407,{"name":92,"@type":93},"Aria Callaghan","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-28","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 is cuproptosis and how is it triggered?","Question",{"text":112,"@type":113},"Cuproptosis is a copper-dependent form of cell death described as being triggered by copper binding to lipoylated enzymes in the tricarboxylic acid cycle, leading to protein aggregation, proteotoxic stress, and ultimately cell death.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How does copper dysregulation affect tumor progression?",{"text":117,"@type":113},"Copper dysregulation has a dual role: it can promote tumor progression through copper-driven cellular growth and proliferation, and it can also suppress tumors by influencing multiple cell-death pathways and immune responses.",{"name":119,"@type":110,"acceptedAnswer":120},"What therapeutic opportunities and biomarkers are discussed for cuproptosis?",{"text":121,"@type":113},"The review summarizes emerging therapeutic approaches targeting copper and cuproptosis, including clinical associations of cuproptosis-related genes and potential biomarkers, while outlining challenges and future prospects for clinical translation.","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},367452,1790531828,{"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":41,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":144},962084926284,"https://ap-avatar.wpscdn.com/davatar_29158cc5080c5b710cf443261637dec0","Signal Transduction [and Targeted Therapy](and Targeted Therapy www.nature.com/sigtrans)[ www.nature.com/sigtrans](and Targeted Therapy www.nature.com/sigtrans)  \nREVIEW ARTICLE  \nOPEN  \nThe molecular mechanism and therapeutic landscape of copper and cuproptosis in cancer  \nZiyu Guo1,2,3,4,5, Danyao Chen6, Lei Yao7, Yuming Sun8, Daishi Li1,2,3,4,5, Jiayuan Le1,2,3,4,5, Yating Dian 1,2,3,4,5, Furong Zeng9 ✉, Xiang Chen 1,2,3,4,5 ✉ and Guangtong Deng 1,2,3,4,5 ✉  \n\n|  | Copper, an essential micronutrient, plays significant roles in numerous biological functions. Recent studies have identified imbalances in copper homeostasis across various cancers, along with the emergence of cuproptosis, a novel copper-dependent form of cell death that is crucial for tumor suppression and therapeutic resistance. As a result, manipulating copper levels has garnered increasing interest as an innovative approach to cancer therapy. In this review, we first delineate copper homeostasis at both cellular and systemic levels, clarifying copper’s protumorigenic and antitumorigenic functions in cancer. We then outline the key milestones and molecular mechanisms of cuproptosis, including both mitochondria-dependent and independent pathways. Next, we explore the roles of cuproptosis in cancer biology, as well as the interactions mediated by cuproptosis between cancer cells and the immune system. We also summarize emerging therapeutic opportunities targeting copper and discuss the clinical associations of cuproptosis-related genes. Finally, we examine potential biomarkers for cuproptosis and put forward the existing challenges and future prospects for leveraging cuproptosis in cancer therapy. Overall, this review enhances our understanding of the molecular mechanisms and therapeutic landscape of copper and cuproptosis in cancer, highlighting the potential of copper-or |  |\n| --- | --- | --- |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n| cuproptosis-based therapies for cancer treatment. |  |  |\n|  | Signal Transduction and Targeted Therapy (2025)10:149 ; [https://doi.org/10.1038/s41392-025-02192-0](https://doi.org/10.1038/s41392-025-02192-0) |  |\n|  |  |  |\n\nINTRODUCTION  \nCopper, an essential trace element crucial for various physiological processes, has garnered increasing attention for its intricate role in cancer biology.1–4 Intracellular copper levels are maintained within a strict range, with even slight elevations potentially causing cytotoxic effects and cell death, emphasizing the need for precise regulation of copper absorption, distribution, and excretion.5–8 In the broader physiological context, copper homeostasis in the human body is primarily maintained through several key processes, including intestinal absorption, vascular transport, hepatic storage, biliary excretion, and utilization and excretion by other organs.9–11 At the cellular level, copper homeostasis involves its uptake and subsequent distribution across various cellular compartments, such as the cytoplasm, mitochondria, Golgi apparatus, and nucleus.12–14 This intricate process encompasses the storage and flux of copper within these organelles, as well as its expulsion from the cell.7,9, 15 The entire sequence of events is coordinated through copper acting as a catalytic cofactor in its redox chemistry, which entails complex interactions with various intracellular enzymes and proteins.16  \nIn the context of cancer, dysregulation of copper metabolism exerts a dual effect on tumor progression. On one hand, cuproplasia, the term that refers to copper-driven cellular growth  \nand proliferation, involves multiple cancer pathways and regulatory mechanisms to promote tumor progression, 17 which could be further accelerated by copper-dependent metastasis, angiogenesis, and immune escape.6, 18–21 On the other hand, copper inhibits tumor growth by participating in the regulation of cell death processes, including apopto","cbCaihnFjW47WNef","https://ap.wps.com/l/cbCaihnFjW47WNef","pdf",5464416,"English","# Introduction\n# Copper homeostasis in cancer\n## Cellular and systemic regulation\n# Cuproptosis mechanisms\n## Mitochondria-dependent and independent pathways\n# Roles in cancer biology and immunity\n## Interactions between cancer cells and the immune system\n# Therapeutic landscape\n## Emerging therapies targeting copper and cuproptosis\n# Clinical associations, biomarkers, and outlook","[{\"question\":\"What is cuproptosis and how is it triggered?\",\"answer\":\"Cuproptosis is a copper-dependent form of cell death described as being triggered by copper binding to lipoylated enzymes in the tricarboxylic acid cycle, leading to protein aggregation, proteotoxic stress, and ultimately cell death.\"},{\"question\":\"How does copper dysregulation affect tumor progression?\",\"answer\":\"Copper dysregulation has a dual role: it can promote tumor progression through copper-driven cellular growth and proliferation, and it can also suppress tumors by influencing multiple cell-death pathways and immune responses.\"},{\"question\":\"What therapeutic opportunities and biomarkers are discussed for cuproptosis?\",\"answer\":\"The review summarizes emerging therapeutic approaches targeting copper and cuproptosis, including clinical associations of cuproptosis-related genes and potential biomarkers, while outlining challenges and future prospects for clinical translation.\"}]","The molecular mechanism and therapeutic landscape of copper and cuproptosis in cancer | PDF",1790170841,76]