[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-detail-349154-en":59,"doc-seo-349154-105":81},{"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":5,"data":60},{"doc_id":61,"user_id":62,"nickname":63,"user_avatar":64,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":66,"doc_content":67,"file_id":68,"file_url":69,"file_type":70,"file_size":71,"view_count":39,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":72,"language":73,"language_code":74,"site_id":75,"html_lang":74,"table_of_contents":76,"faqs":77,"seo_title":78,"seo_description":66,"update_tm":79,"read_time":80},349154,1374402968488,"Đào","https://ap-avatar.wpscdn.com/davatar_29158cc5080c5b710cf443261637dec0","A fistful of iron - ferritin as a vulnerability point of the brain cancers - review article","Iron metabolism is increasingly linked to cancer development and progression, since iron is required for essential cellular processes but can also drive reactive-oxygen-species toxicity. Ferritin coordinates iron homeostasis and emerges as a therapeutic target because it buffers cellular iron levels. This review examines how ferritin shapes brain cancer biology in tumor cells and cancer stem cells, which resist standard treatment. It highlights ferritin’s roles in oxidative-stress protection and ferroptosis resistance, and discusses ferritin-targeting strategies, including ferritinophagy inducers and redox-based therapies that exploit CSC iron dependence for iron-dependent cell death and improved outcomes.","[www.nature.com/cddis](www.nature.com/cddis)  \nREVIEW ARTICLE OPEN   \nA fistful of iron: ferritin as a vulnerability point of the brain cancers  \nFabien Segui1, Scott Kenneth Parks2, Milica Vucetic 1 ✉ and Vincent Picco 1 ✉  \n© The Author(s) 2026  \n|  |  |  |\n| --- | --- | --- |\n|  | Iron metabolism is increasingly recognized as a key player in the development and progression of various cancers. Iron is required for vital cellular processes such as energy production; however, it can also interact with reactive oxygen species to cause cellular toxicity. Consequently, a host of proteins coordinate iron homeostasis, and ferritin stands out as a promising therapeutic target due to its pivotal role in buffering cellular iron levels. This review explores the relevance of ferritin in brain cancers, shedding light on how it influences the biology of both tumor cells and cancer stem cells (CSCs), a population of tumor cells that is notable in their resistance to conventional treatment strategies. Ferritin plays a critical role in protecting against oxidative stress and boosting resistance to ferroptosis, a form of cell death often evaded by CSCs. Development of cutting-edge strategies designed to target ferritin, including ferritinophagy-inducing compounds and novel redox-based therapies that can capitalize on the iron dependency of CSCs is discussed in context. We propose that the iron addiction of brain cancer cells provides a specific susceptibility, whereby removing their iron buffering mechanism via targeting of ferritin can result in favorable treatment outcomes, including the induction of iron-dependent cell death. Future studies on the modulation of ferritin offer a ground-breaking therapeutic strategy to undermine CSC-driven tumor growth, overcome resistance to conventional therapies, and ultimately improve treatment outcomes |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n| for patients battling brain cancers. |  |  |\n|  | Cell Death and Disease (2026)17:451; [https://doi.org/10.1038/s41419-026-08564-w](https://doi.org/10.1038/s41419-026-08564-w) |  |\n|  |  |  |\n\nKEY FACTS  \n● Brain cancer cells (including cancer stem cells (CSCs)) from glioblastoma (GBM) and medulloblastoma (MB), rely on high iron uptake and storage to support proliferation, survival, and stemness and thus exhibit an “iron addiction”.  \n● Ferritin is the primary intracellular iron storage and buffering system, protecting brain CSCs from ironinduced oxidative stress and ferroptosis.  \n● Elevated ferritin expression in brain tumor cells correlates with higher tumor grade, CSC maintenance, resistance to therapeutics, and worse patient prognosis, highlighting its role in tumor aggressiveness.  \n● Targeting ferritin via ferritinophagy inducers (e.g., NCOA4 modulation, MMRi compounds, high-dose vitamin C) can elevate labile iron, generate ROS, and sensitize brain cancer cells—particularly CSCs—to ferroptosis or other irondependent cell death pathways.  \n● Modulation of ferritin may enhance the efficacy of conventional therapies (radiotherapy, chemotherapy) by increasing ROS-mediated cytotoxicity, overcoming CSCdriven resistance, and reducing tumor relapse.  \nOPEN QUESTIONS  \n● How can ferritin-targeted therapies selectively induce ferroptosis in brain CSCs without causing neurotoxicity in normal neurons or glial cells?  \n● What are the precise molecular mechanisms by which ferritin levels regulate CSC stemness, proliferation, and survival in brain tumors?  \n● How do different subtypes of brain CSCs (e.g., embryonic-like vs. epithelial-like origins) respond to ferritin modulation, and how does this affect therapy outcomes?  \n● Which strategies can improve blood–brain barrier (BBB) penetration and CNS bioavailability for ferritin-targeting compounds while maintaining tumor specificity?  \n● Can ferritin expression or labile iron levels serve as predictive biomarkers for patient stratification and","cbCaijrpKnJq3qaN","https://ap.wps.com/l/cbCaijrpKnJq3qaN","pdf",1441906,13,"English","en",105,"# Key Facts\n# Open Questions\n# Introduction\n## Ferroptosis mechanism and ferritin’s role","[{\"question\":\"Why is ferritin considered a promising therapeutic target in brain cancers?\",\"answer\":\"Ferritin buffers cellular iron levels and helps protect cancer stem cells from iron-induced oxidative stress and ferroptosis. Elevated ferritin expression is associated with higher tumor grade, therapeutic resistance, and poorer prognosis.\"},{\"question\":\"How do brain cancer cells develop “iron addiction”?\",\"answer\":\"Brain cancer cells, including cancer stem cells in glioblastoma and medulloblastoma, rely on high iron uptake and storage to support proliferation, survival, and stemness. This dependence makes them vulnerable to disruptions in iron handling.\"},{\"question\":\"What approaches are proposed to target ferritin and sensitize cells to ferroptosis?\",\"answer\":\"The review discusses ferritin-targeting strategies such as ferritinophagy inducers, including NCOA4 modulation, MMRi compounds, and high-dose vitamin C, which can increase labile iron and ROS to sensitize cells—especially CSCs—to ferroptosis or other iron-dependent death pathways.\"}]","A fistful of iron - ferritin as a vulnerability point of the brain cancers - review article | PDF",1790081989,33,{"code":4,"msg":82,"data":83},"ok",{"site_id":75,"language":74,"slug":84,"title":65,"keywords":85,"description":66,"schema_data":86,"social_meta":140,"head_meta":142,"extra_data":144,"updated_unix":145},"a-fistful-of-iron-ferritin-as-a-vulnerability-point-of-the-brain-cancers-review-article","",{"@graph":87,"@context":139},[88,102,122],{"@type":89,"itemListElement":90},"BreadcrumbList",[91,95,97,100],{"item":92,"name":93,"@type":94,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":96,"name":9,"@type":94,"position":14},"https://docshare.wps.com/document/",{"item":98,"name":35,"@type":94,"position":99},"https://docshare.wps.com/document/healthcare/",3,{"item":101,"name":65,"@type":94,"position":19},"https://docshare.wps.com/document/a-fistful-of-iron-ferritin-as-a-vulnerability-point-of-the-brain-cancers-review-article/349154/",{"url":101,"name":65,"@type":103,"image":104,"author":109,"headline":65,"publisher":111,"fileFormat":114,"inLanguage":74,"description":66,"dateModified":115,"datePublished":116,"encodingFormat":114,"isAccessibleForFree":117,"interactionStatistic":118},"DigitalDocument",{"url":105,"@type":106,"width":107,"height":108},"https://docshare.wps.com/thumbnails/a-fistful-of-iron-ferritin-as-a-vulnerability-point-of-the-brain-cancers-review-article/349154.png","ImageObject",300,407,{"name":63,"@type":110},"Person",{"url":92,"name":112,"@type":113},"DocShare","Organization","application/pdf","2026-10-30","2026-09-22",true,{"@type":119,"interactionType":120,"userInteractionCount":39},"InteractionCounter",{"@type":121},"ViewAction",{"@type":123,"mainEntity":124},"FAQPage",[125,131,135],{"name":126,"@type":127,"acceptedAnswer":128},"Why is ferritin considered a promising therapeutic target in brain cancers?","Question",{"text":129,"@type":130},"Ferritin buffers cellular iron levels and helps protect cancer stem cells from iron-induced oxidative stress and ferroptosis. Elevated ferritin expression is associated with higher tumor grade, therapeutic resistance, and poorer prognosis.","Answer",{"name":132,"@type":127,"acceptedAnswer":133},"How do brain cancer cells develop “iron addiction”?",{"text":134,"@type":130},"Brain cancer cells, including cancer stem cells in glioblastoma and medulloblastoma, rely on high iron uptake and storage to support proliferation, survival, and stemness. This dependence makes them vulnerable to disruptions in iron handling.",{"name":136,"@type":127,"acceptedAnswer":137},"What approaches are proposed to target ferritin and sensitize cells to ferroptosis?",{"text":138,"@type":130},"The review discusses ferritin-targeting strategies such as ferritinophagy inducers, including NCOA4 modulation, MMRi compounds, and high-dose vitamin C, which can increase labile iron and ROS to sensitize cells—especially CSCs—to ferroptosis or other iron-dependent death pathways.","https://schema.org",{"og:url":101,"og:type":141,"og:title":65,"og:site_name":112,"og:description":66},"article",{"robots":143,"canonical":101},"index,follow",{"doc_id":61,"site_id":75},1790154884]