[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-371965-105":3,"detail-sidebar-cat-0-en-105":81,"doc-detail-371965-en":130},{"code":4,"msg":5,"data":6},0,"ok",{"site_id":7,"language":8,"slug":9,"title":10,"keywords":11,"description":12,"schema_data":13,"social_meta":74,"head_meta":76,"extra_data":78,"updated_unix":80},105,"en","ferroptosis-and-cancer-when-iron-turns-against-tumors","Ferroptosis and cancer: when iron turns against tumors","","Ferroptosis is an iron-dependent regulated necrosis driven by uncontrolled lipid peroxidation, increasingly recognized as central to cancer biology. Chronic ferric nitrilotriacetate (Fe-NTA) exposure in a rat model links Fenton chemistry to DNA damage, genomic instability, and selection of ferroptosis-resistant malignant clones. Cancer cells also rewire iron handling and antioxidant programs to escape ferroptotic pressure. Ferroptosis can further function as immunogenic death via oxidized phospholipids and DAMP release that activates dendritic cells and CD8+ T cells, including immunoferroptosis. Low-temperature plasma selectively triggers ferroptosis in iron-loaded tumors.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/healthcare/","Healthcare",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/ferroptosis-and-cancer-when-iron-turns-against-tumors/371965/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/ferroptosis-and-cancer-when-iron-turns-against-tumors/371965.png","ImageObject",300,407,{"name":42,"@type":43},"dhado","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-11-02","2026-09-23",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",10,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"What is ferroptosis and what drives it?","Question",{"text":63,"@type":64},"Ferroptosis is an iron-dependent form of regulated necrosis driven by unchecked lipid peroxidation. The process links iron availability to destructive oxidative damage in cells.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How do cancer cells adapt to resist ferroptosis?",{"text":68,"@type":64},"Cancer cells reinforce iron acquisition and antioxidant defenses while escaping ferroptotic pressure. The text highlights pathways such as xCT–CD44v, GPX4/FSP1 activity, NRF2-mediated antioxidant programs, and mitochondrial remodeling.",{"name":70,"@type":61,"acceptedAnswer":71},"What does immunoferroptosis mean and how can it be induced?",{"text":72,"@type":64},"Immunoferroptosis refers to ferroptosis acting as an immunogenic cell death mode by releasing oxidized phospholipids and DAMPs that activate dendritic cells and CD8+ T cells. Low-temperature plasma is presented as a modality that can selectively trigger ferroptosis in iron-loaded cancer cells.","https://schema.org",{"og:url":32,"og:type":75,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":77,"canonical":32},"index,follow",{"doc_id":79,"site_id":7},371965,1790342900,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,110,115,120,123,126],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":85,"show_sort_weight":86,"slug":87},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":89,"show_sort_weight":90,"slug":91},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":93,"show_sort_weight":94,"slug":95},"Exam",70,"exam",{"id":97,"doc_module":4,"doc_module_name":25,"category_name":98,"show_sort_weight":99,"slug":100},5,"Comic",60,"comic",{"id":102,"doc_module":4,"doc_module_name":25,"category_name":103,"show_sort_weight":104,"slug":105},6,"Technology",50,"technology",{"id":107,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":108,"slug":109},7,40,"healthcare",{"id":111,"doc_module":4,"doc_module_name":25,"category_name":112,"show_sort_weight":113,"slug":114},8,"Research & Report",30,"research-report",{"id":116,"doc_module":4,"doc_module_name":25,"category_name":117,"show_sort_weight":118,"slug":119},9,"Religion & Spirituality",20,"religion-spirituality",{"id":118,"doc_module":4,"doc_module_name":25,"category_name":121,"show_sort_weight":118,"slug":122},"World Cup","world-cup",{"id":55,"doc_module":4,"doc_module_name":25,"category_name":124,"show_sort_weight":55,"slug":125},"Lifestyle","lifestyle",{"id":127,"doc_module":4,"doc_module_name":25,"category_name":128,"show_sort_weight":97,"slug":129},19,"General","general",{"code":4,"msg":82,"data":131},{"doc_id":79,"user_id":132,"nickname":42,"user_avatar":133,"doc_module":4,"category_id":107,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":139,"language":140,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":12,"update_tm":144,"read_time":145},5909893218464,"https://ap-avatar.wpscdn.com/davatar_085a072bc5b1113ac321206ff7593b45","Cellular and Molecular Life Sciences (2026) 83:16  \n[https://doi.org/10.1007/s00018-025-05982-5](https://doi.org/10.1007/s00018-025-05982-5) Cellular and Molecular Life Sciences  \nREVIEW  \nFerroptosis and cancer: when iron turns against tumors  \nShinya Toyokuni1,2,3 · Yingyi Kong1 · Yuki Maeda1 · Qinying Lyu1 · Yuuki Ohara1,4 · Kotaro Sato1,5 · Yashiro Motooka1 · Kae Nakamura2,3 · Hiromasa Tanaka2,3  \nReceived: 11 July 2025 / Revised: 21 October 2025 / Accepted: 2 November 2025 © The Author(s) 2025  \nAbstract  \nBackground Ferroptosis is an iron-dependent form of regulated necrosis driven by unchecked lipid peroxidation. Its relevance to cancer biology has become increasingly evident. Our long-standing ferric nitrilotriacetate (Fe-NTA) rat model exemplifies how chronic Fenton chemistry induces DNA damage, genomic instability, and selection of ferroptosis-resistant malignant clones, underscoring the central role ofiron in carcinogenesis.  \nRecent Advances Cancer cells acquire multiple adaptations to maintain iron addiction while escaping ferroptotic pressure, including reinforcement of the xCT–CD44v axis, GPX4 and FSP1 activities, NRF2-mediated antioxidant programs, and mitochondrial remodeling. Ferroptosis can also act as an immunogenic cell death modality by releasing oxidized phospholipids and DAMPs that activate dendritic cells and CD8⁺ T cells, a process termed immunoferroptosis. Low-temperature plasma (LTP) has emerged as a unique modality capable of producing reactive oxygen and nitrogen species to selectively trigger ferroptosis in iron-loaded cancer cells while sparing normal tissues.  \nDiagnostic and Genetic Context HNE-modified proteins currently serve as robust markers of lipid peroxidation in FFPE samples, whereas visualization of catalytic Fe(II)—the executer offerroptosis—requires frozen tissues or live-cell imaging. Cancer-prone hereditary syndromes such as BRCA1/2 deficiency and Fanconi anemia exhibit ferroptosis resistance, linking defective genome maintenance to impaired ferroptotic signaling.  \nOutlook Ferroptosis functions both as an intrinsic tumor-suppressive mechanism and a tractable therapeutic vulnerability. Harnessing ferroptosis offers a promising strategy for targeting iron-addicted cancers.  \nKeywords Ferric nitrilotriacetate (Fe-NTA) · Kidney · Nanomaterial · HNEJ-1 · Ferritin · Plasma activated lactated ringer’s solution (PAL) · PCBP2  \n􀀍 Shinya Toyokuni [toyokuni@med.nagoya-u.ac.jp](toyokuni@med.nagoya-u.ac.jp)  \n1 Department of Pathology and Biological Responses, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan  \n2 Center for Low Temperature Plasma Sciences, Nagoya University, Furo-cho, Chikusa, Nagoya 464-8603, Japan  \n3 Center for Integrated Sciences ofLow-temperature Plasma Core Research (iPlasma Core), Tokai National Higher Education and Research System, Furo-Cho, Chikusa-ku, Nagoya 464-8603, Japan  \n4 Institute for Advanced Research (IAR), Nagoya University , Furo-Cho, Chikusa-ku, Nagoya 464-8601, Japan  \n5 Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan  \nAbbreviations  \nACSL4 Acyl CoA synthetase long-chain family member 4  \nDHODH Dihydroorotate dehydrogenase  \nELOVL5 Elongation of very long chain fatty acids protein 5  \nFADS2 Fatty acid desaturase 2  \nFe-NTA Ferric nitrilotriacetate  \nFFPE Formalin-fixed paraffin-embedded (-ing)  \nGPX4 Glutathione peroxidase 4  \nGSH Glutathione, reduced form  \nHNE 4-Hydroxy-2-nonenal  \nIHC Immunohistochemistry (-ical)  \nLPCAT3 Lysophosphatidylcholine acyltransferase 3 LTP Low-temperature plasma  \nMUFAs Monounsaturated fatty acids 8-OHdG 8-Hydroxy-2’-deoxyguanosine  \n1 3  \nPAL Plasma-activated lactated Ringer’s solution, or  \nplasma-activated liquid  \nPAM Plasma-activated medium  \nPARP Poly(ADP-ribose) polymerase PUFA Polyunsaturated fatty acid RCC Renal cell carcinoma  \nROS Reactive oxygen species  \nSCD1 Stearoyl-CoA Desaturase TAMs Tumor-associated ","cbCaicqiox9Km7hv","https://ap.wps.com/l/cbCaicqiox9Km7hv","pdf",6196181,23,"English","# Abstract\n# Background\n# Recent Advances\n## Adaptations enabling ferroptosis escape\n## Immunogenic cell death and immunoferroptosis\n## Low-temperature plasma triggering ferroptosis\n# Diagnostic and Genetic Context\n# Outlook\n# Abbreviations","[{\"question\":\"What is ferroptosis and what drives it?\",\"answer\":\"Ferroptosis is an iron-dependent form of regulated necrosis driven by unchecked lipid peroxidation. The process links iron availability to destructive oxidative damage in cells.\"},{\"question\":\"How do cancer cells adapt to resist ferroptosis?\",\"answer\":\"Cancer cells reinforce iron acquisition and antioxidant defenses while escaping ferroptotic pressure. The text highlights pathways such as xCT–CD44v, GPX4/FSP1 activity, NRF2-mediated antioxidant programs, and mitochondrial remodeling.\"},{\"question\":\"What does immunoferroptosis mean and how can it be induced?\",\"answer\":\"Immunoferroptosis refers to ferroptosis acting as an immunogenic cell death mode by releasing oxidized phospholipids and DAMPs that activate dendritic cells and CD8+ T cells. Low-temperature plasma is presented as a modality that can selectively trigger ferroptosis in iron-loaded cancer cells.\"}]","Ferroptosis and cancer: when iron turns against tumors | PDF",1790193335,58]