[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-351395-105":59,"doc-detail-351395-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","a-clinical-decision-framework-for-redox-adapted-emt-high-cancers-from-ferroptosis-resistance-to-precision-therapeutic-stratification","A clinical decision framework for redox-adapted, EMT-high cancers: From ferroptosis resistance to precision therapeutic stratification","","Therapeutic resistance in advanced solid tumors increasingly reflects the emergence of adaptive tumor states rather than the absence of actionable molecular targets. This work proposes a state-based redox–EMT framework that translates ferroptosis resistance, EMT-driven plasticity, metabolic rewiring, immune evasion, and extracellular vesicle communication into clinical decision rules. It emphasizes an NRF2-centered antioxidant buffering and multilayered ferroptosis defense resistance axis and defines actionable biomarker-guided stratification using tissue and liquid biopsy markers for dynamic monitoring and trial design in PDAC and beyond.",{"@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":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/a-clinical-decision-framework-for-redox-adapted-emt-high-cancers-from-ferroptosis-resistance-to-precision-therapeutic-stratification/351395/",{"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/a-clinical-decision-framework-for-redox-adapted-emt-high-cancers-from-ferroptosis-resistance-to-precision-therapeutic-stratification/351395.png","ImageObject",300,407,{"name":92,"@type":93},"Maya Linwood","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-09-23","2026-09-22",true,{"@type":102,"interactionType":103,"userInteractionCount":8},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What problem does the paper address in advanced solid tumors?","Question",{"text":112,"@type":113},"It addresses therapeutic resistance that arises from adaptive tumor states, which can outcompete actionable molecular targets rather than reflecting a total lack of targets.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How does the framework connect redox adaptation to clinical decision-making?",{"text":117,"@type":113},"It translates redox–EMT adaptive programs into clinical decision rules for patient stratification, therapeutic sequencing, and trial design based on measurable biomarkers.",{"name":119,"@type":110,"acceptedAnswer":120},"Which biomarkers and readouts are proposed for stratifying redox states?",{"text":121,"@type":113},"The paper links ferroptosis defense markers such as GPX4, SLC7A11, and FSP1, NRF2 activity, EMT status, and host metabolic context, using tissue and liquid biopsy readouts including circulating tumor DNA, exosomal PD-L1, and redox-responsive microRNAs.","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},351395,1790200308,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":8,"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},962084928432,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","Redox Biology 92 (2026) 104111  \nContents lists available at ScienceDirect  \nRedox Biology  \njournal [homepage:](homepage: www.elsevier.com/locate/redox)[ www.elsevier.com/locate/redox](homepage: www.elsevier.com/locate/redox)  \n| A clinical decision framework for redox-adapted, EMT-high cancers: From ferroptosis resistance to precision therapeutic stratification\u003Cbr>Moon Nyeo Parka, Hyo Jeong Kim a, Sohyun Parka, Rony Abdi Syahputrab, Domenico V. Delfino c, Seong-Gyu Koa,d,*, Bonglee Kim a,d,**\u003Cbr>a College of Korean Medicine, Kyung Hee University, 1-5 Hoegidong, Dongdaemun-gu, Seoul, 02447, Republic of Korea b Department of Pharmacology, Faculty of Pharmacy, Universitas Sumatera Utara, Medan, Sumatera Utara, 20155, Indonesia c Department of Medicine and Surgery, Piazza Universit`a 1, Perugia, 06123, Italy\u003Cbr>d Korean Medicine-Based Drug Repositioning Cancer Research Center, College of Korean Medicine, Kyung Hee University, Hoegi-dong Dongdaemun-gu, Seoul, 02447, Republic of Korea |  |  |\n| --- | --- | --- |\n| A R T I C L E I N F O |  | A B S T R A C T |\n| Keywords:\u003Cbr>Redox adaptation Ferroptosis resistance NRF2 signaling State-based oncology\u003Cbr>Biomarker-guided stratification Type 2 diabetes–associated cancer |  | Therapeutic resistance in advanced solid tumors increasingly reflects the emergence of adaptive tumor states rather than the absence of actionable molecular targets. Among these, redox adaptation represents a clinically decisive program that integrates ferroptosis resistance, epithelial–mesenchymal transition (EMT)–driven plasticity, metabolic rewiring, immune evasion, and extracellular vesicle–mediated communication. Here, we propose a state-based redox–EMT framework that explicitly translates these adaptive programs into clinical decision rules for patient stratification, therapeutic sequencing, and trial design. We synthesize mechanistic and translational evidence demonstrating that NRF2-centered antioxidant buffering and multilayered ferroptosis defense constitute an independent resistance axis that frequently supersedes oncogene dependency, particularly in metabolically compromised hosts such as patients with type 2 diabetes–associated pancreatic ductal adenocarcinoma (PDAC). Building on this concept, we delineate discrete redox–EMT tumor states, ranging from redoxlow, EMT-restricted phenotypes to terminal redox-locked ecosystems characterized by ferroptosis resistance, stromal insulation, and immune exclusion. Importantly, we translate these states into actionable clinical decision rules, linking ferroptosis defense markers (e.g., GPX4, SLC7A11, FSP1), NRF2 activity, EMT status, and host metabolic context to rational selection and sequencing of cytotoxic therapy, targeted agents, redox modulation, and immunotherapy. We further outline a biomarker-guided stratification strategy integrating tissue-based and liquid biopsy readouts, including circulating tumor DNA, exosomal PD-L1, and redox-responsive microRNAs, to enable dynamic monitoring of tumor redox states during treatment. By reframing redox adaptation as a measurable, stratifiable, and targetable tumor state, this work provides a decision-oriented roadmap for stateaware precision oncology. Collectively, our framework supports a shift from mutation-centric treatment escalation toward clinical algorithms that anticipate and intercept redox-adapted therapeutic resistance, with direct implications for biomarker-enriched trials and adaptive treatment strategies in PDAC and beyond. |\n\n1. Introduction  \n1.1. Therapeutic failure as a consequence of host-conditioned redoxadapted tumor states  \nCancer treatment has advanced substantially over recent decades; however, durable responses remain elusive in many solid tumors due to  \nthe emergence of adaptive resistance programs that transcend individual drug classes. Accumulating evidence indicates that redox adaptation constitutes a unifying biological framework through which cancer cells evade cytotoxic, targeted, an","cbCaikLK20DWz5zx","https://ap.wps.com/l/cbCaikLK20DWz5zx","pdf",3675979,15,"English","# Introduction\n## Therapeutic failure as a consequence of host-conditioned redox-adapted tumor states","[{\"question\":\"What problem does the paper address in advanced solid tumors?\",\"answer\":\"It addresses therapeutic resistance that arises from adaptive tumor states, which can outcompete actionable molecular targets rather than reflecting a total lack of targets.\"},{\"question\":\"How does the framework connect redox adaptation to clinical decision-making?\",\"answer\":\"It translates redox–EMT adaptive programs into clinical decision rules for patient stratification, therapeutic sequencing, and trial design based on measurable biomarkers.\"},{\"question\":\"Which biomarkers and readouts are proposed for stratifying redox states?\",\"answer\":\"The paper links ferroptosis defense markers such as GPX4, SLC7A11, and FSP1, NRF2 activity, EMT status, and host metabolic context, using tissue and liquid biopsy readouts including circulating tumor DNA, exosomal PD-L1, and redox-responsive microRNAs.\"}]","A clinical decision framework for redox-adapted, EMT-high cancers: From ferroptosis resistance to precision therapeutic stratification | PDF",1790093989,38]