[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-456745-105":3,"detail-sidebar-cat-0-en-105":81,"doc-detail-456745-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","targeting-fsp1-triggers-ferroptosis-in-lung-cancer-open-access","Targeting FSP1 triggers ferroptosis in lung cancer - Open access","","Emerging evidence suggests cancer cells are vulnerable to ferroptosis, an iron- and lipid-peroxidation–driven cell death. Using genetically engineered mouse models of lung adenocarcinoma, researchers performed tumour-specific loss-of-function studies of GPX4 and FSP1 pathway regulators and found increased lipid peroxidation with robust tumorigenesis suppression. In vivo, FSP1 was required for ferroptosis protection, while knockout lipid peroxide accumulation and ferroptosis inhibition restored tumor growth. FSP1 expression (AIFM2) predicted progression and poorer survival, and pharmacologic FSP1 inhibition provided therapeutic benefit across pre-clinical lung cancer models.",{"@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/targeting-fsp1-triggers-ferroptosis-in-lung-cancer-open-access/456745/",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/targeting-fsp1-triggers-ferroptosis-in-lung-cancer-open-access/456745.png","ImageObject",300,407,{"name":42,"@type":43},"Lucas Martin","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-31","2026-09-30",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 role does FSP1 play in ferroptosis protection in lung cancer models?","Question",{"text":63,"@type":64},"FSP1 was required for ferroptosis protection in vivo, even though this protection did not hold in vitro.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How do Fsp1-knockout tumors respond in lipidomic analyses?",{"text":68,"@type":64},"Fsp1-knockout tumors accumulated lipid peroxides, consistent with impaired suppression of lipid peroxidation.",{"name":70,"@type":61,"acceptedAnswer":71},"Why is FSP1 considered a potential therapeutic target for lung adenocarcinoma?",{"text":72,"@type":64},"FSP1 expression (AIFM2) was prognostic for disease progression and poorer survival, and pharmacologic inhibition of FSP1 showed therapeutic benefit in pre-clinical models.","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},456745,1790867123,{"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":99,"preview_page_count":4},8796095360427,"https://ap-avatar.wpscdn.com/davatar_994ba38a5ba835b3df7d355c54d3ed8d","Article  \n\n| Targeting FSP1 triggers ferroptosisin lung cancer |  |  |\n| --- | --- | --- |\n| [https://doi.org/10.1038/s41586-025-09710-8](https://doi.org/10.1038/s41586-025-09710-8)\u003Cbr>Received: 25 August 2024 Accepted: 6 October 2025 Published online: 5 November 2025 Open access\u003Cbr> Check for updates | Katherine Wu1,2,12, Alec J. Vaughan1,2,12, Jozef P. Bossowski1,3, Yuan Hao1,3, Aikaterini Ziogou1,3, Seon Min Kim4, Tae Ha Kim4, Mari N. Nakamura1,3, Ray Pillai1,5,6, Mariana Mancini1,3,\u003Cbr>Sahith Rajalingam1,3, Mingqi Han7,8, Toshitaka Nakamura9, Lidong Wang10, Suckwoo Chung1,3, Diane Simeone10, David Shackelford7,8, Yun Pyo Kang4, Marcus Conrad9,11 &\u003Cbr>Thales Papagiannakopoulos1,3 ✉\u003Cbr>Emerging evidence indicates that cancer cells are susceptible to ferroptosis, a form of cell death that is triggered by uncontrolled lipid peroxidation1–3. Despite broad enthusiasm about harnessing ferroptosis asa novel anti-cancer strategy, whether ferroptosisis a barrier to tumorigenesis and can be leveraged therapeutically remains unknown4,5. Here, using genetically engineered mouse models of lung adenocarcinoma, we performed tumour-specific loss-of-function studies of two key ferroptosis suppressors, GPX46,7 and ferroptosis suppressor protein 1 (FSP1)8,9, and observed increased lipid peroxidation and robust suppression of tumorigenesis, suggesting that lung tumours are highly sensitive to ferroptosis. Furthermore, across multiple pre-clinical models, we found that FSP1 was required for ferroptosis protection in vivo, but not in vitro, underscoring a heightened need to buffer lipid peroxidation under physiological conditions. Lipidomic analyses revealed that Fsp1-knockout tumours had an accumulation of lipid peroxides, and inhibition offerroptosis with genetic, dietary orpharmacological approaches effectively restored the growth ofFsp1-knockout tumoursin vivo. Unlike GPX4, expression ofFSP1 (also known asAIFM2) was prognostic for disease progression and poorer survival inpatients with lung adenocarcinoma, highlighting its potential asa viable therapeutic target. To this end, we demonstrated that pharmacologic inhibition ofFSP1 had significant therapeutic benefit in pre-clinical lung cancer models. Our studies highlight the importance offerroptosis suppression in vivo and pave the way for FSP1 inhibition asa therapeutic strategy for patients with lung cancer. |  |\n| Ferroptosisis anon-apoptotic, oxidative stress-dependent mechanism |  | cells can be sensitized to ferroptosis through PUFA-PL composition16 |\n| of cell death that is uniquely distinguished by lipid peroxidation of |  | and biosynthesis by ACSL417–19. In addition to these cellular pathways, |\n| polyunsaturated fatty acids of membrane phospholipids (PUFA-PLs)1,10. |  | exogenous lipid RTAs, such as LIP1, FER1, vitamin E and vitamin K, have |\n| Lipid peroxidation involves the formation of lipid and lipid peroxyl |  | also been shown to specifically inhibit ferroptosis1,6,20–22. |\n| radicals, which, in auto-oxidative propagation reactions, generate |  | Emerging evidence indicates that cancer cells, including drug- |\n| lipid hydroperoxides. Aberrant, unrestricted lipid peroxidation results |  | resistant cells that have adopted a mesenchymal state2,3, are highly |\n| in altered membrane integrity, cell swelling, and ultimately mem- |  | sensitive to lipid peroxidation in vitro, suggesting a potential for har- |\n| brane rupture11,12. In recent years, growing interest in ferroptosis has |  | nessing ferroptosis asa novel anti-cancer strategy. Although there have |\n| revealed that cells depend on several enzymes to protect against fer- |  | been extensive studies characterizing GPX4 and more recently FSP1 in |\n| roptosis6–9,13–15, of which GPX4 and FSP1 have key roles. GPX4 catalyses |  | various diseases4,23, whether ferroptosis constitutes a barrier totumo- |\n| the reduction of PUFA-PL hydroperoxidesto non-toxic alcohols. FSP1 |  | rigenesis and the functional roles of GPX4 and FSP1 i","cbCaiad7pQR00oDC","https://ap.wps.com/l/cbCaiad7pQR00oDC","pdf",16868088,24,"English","# Background\n## Ferroptosis and lipid peroxidation\n## GPX4 and FSP1 roles\n# Experimental approach\n## Genetically engineered lung cancer models\n## Tumour-specific loss-of-function studies\n# Key findings\n## FSP1 requirement in vivo but not in vitro\n## Lipidomic changes and rescue by ferroptosis inhibition\n## Prognostic value of FSP1 (AIFM2)\n# Therapeutic implications\n## Pharmacologic inhibition of FSP1","[{\"question\":\"What role does FSP1 play in ferroptosis protection in lung cancer models?\",\"answer\":\"FSP1 was required for ferroptosis protection in vivo, even though this protection did not hold in vitro.\"},{\"question\":\"How do Fsp1-knockout tumors respond in lipidomic analyses?\",\"answer\":\"Fsp1-knockout tumors accumulated lipid peroxides, consistent with impaired suppression of lipid peroxidation.\"},{\"question\":\"Why is FSP1 considered a potential therapeutic target for lung adenocarcinoma?\",\"answer\":\"FSP1 expression (AIFM2) was prognostic for disease progression and poorer survival, and pharmacologic inhibition of FSP1 showed therapeutic benefit in pre-clinical models.\"}]","Targeting FSP1 triggers ferroptosis in lung cancer - Open access | PDF",1790746914]