[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-353129-105":3,"detail-sidebar-cat-0-en-105":81,"doc-detail-353129-en":131},{"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-chemotherapy-resistance-in-ovarian-cancer-molecular-mechanismsand-therapeutic-opportunities","Ferroptosis and chemotherapy resistance in ovarian cancer: molecular mechanismsand therapeutic opportunities","","Ovarian cancer remains the most lethal gynecologic malignancy, and acquired platinum resistance drives most treatment failures. This review analyzes how ferroptosis, an iron-dependent regulated cell death driven by lipid peroxidation, forms a metabolic vulnerability in high-grade serous ovarian cancer that resistant tumors cannot fully evade. It connects ferroptosis pathways such as the GPX4 antioxidant axis, polyunsaturated fatty acid biosynthesis, and iron homeostasis with chemotherapy resistance. The synthesis highlights mechanisms and translational challenges, including therapeutic opportunities like BRCA1-linked GPX4 regulation, stromal protection by CAFs, and the need for validated predictive biomarkers.",{"@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-chemotherapy-resistance-in-ovarian-cancer-molecular-mechanismsand-therapeutic-opportunities/353129/",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-chemotherapy-resistance-in-ovarian-cancer-molecular-mechanismsand-therapeutic-opportunities/353129.png","ImageObject",300,407,{"name":42,"@type":43},"Jasmine","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-30","2026-09-22",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",14,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"What problem does the review focus on in ovarian cancer treatment?","Question",{"text":63,"@type":64},"The review focuses on acquired platinum resistance, which accounts for most treatment failures and leads to relapse in advanced disease.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How is ferroptosis described, and why is it relevant to therapy resistance?",{"text":68,"@type":64},"Ferroptosis is an iron-dependent regulated cell death driven by lipid peroxidation. The review argues it creates a metabolic vulnerability that therapy-resistant cancers cannot fully evade.",{"name":70,"@type":61,"acceptedAnswer":71},"Which ferroptosis-related mechanisms are analyzed in relation to chemotherapy resistance?",{"text":72,"@type":64},"The review examines the GPX4 antioxidant axis, polyunsaturated fatty acid biosynthesis, and iron homeostasis, and highlights findings such as BRCA1-dependent GPX4 regulation and NR1D2-mediated repression of FSP1.","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},353129,1790155844,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,110,115,120,123,127],{"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":124,"doc_module":4,"doc_module_name":25,"category_name":125,"show_sort_weight":124,"slug":126},10,"Lifestyle","lifestyle",{"id":128,"doc_module":4,"doc_module_name":25,"category_name":129,"show_sort_weight":97,"slug":130},19,"General","general",{"code":4,"msg":82,"data":132},{"doc_id":79,"user_id":133,"nickname":42,"user_avatar":134,"doc_module":4,"category_id":107,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":124,"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},2336478487870,"https://ap-avatar.wpscdn.com/davatar_085a072bc5b1113ac321206ff7593b45","Li etal. Journal of Ovarian Research (2026) 19:220 Journal of Ovarian Research  \n[https://doi.org/10.1186/s13048-026-02150-6](https://doi.org/10.1186/s13048-026-02150-6)  \nREVIEW Open Access  \nFerroptosis and chemotherapy resistance in ovarian cancer: molecular mechanismsand therapeutic opportunities  \nShuqing Li1*, Lina Yang2 and Zhiling Zhu1*  \nAbstract  \nOvarian cancer remains the most lethal gynecologic malignancy, with acquired platinum resistance accounting for the majority of treatment failures. Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, has emerged as a metabolic vulnerability that therapy-resistant cancers cannot fully evade. This review examines the relationship between ferroptosis and chemotherapy resistance in high-grade serous ovarian cancer (HGSOC), analyzing the GPX4 antioxidant axis, polyunsaturated fatty acid biosynthesis, and iron homeostasis. We highlight recent discoveries including BRCA1-dependent ubiquitination of GPX4 and its implications for PARP inhibitor synthetic lethality, NR1D2-mediated transcriptional repression of FSP1, and stromal protection conferred by cancer-associated fibroblasts. The unique features of ovarian cancer—iron-abundant ascites, the lipid-rich omental niche, and prevalent BRCA mutations—present distinctive therapeutic opportunities. We introduce the novel concepts of a “ferroptosis compensatory threshold” requiring concurrent multi-node inhibition, and the need for personalized therapeutic design based on tumor ferroptosis defense profiling. We also address challenges confronting clinical translation: on-target toxicities, resistance mechanisms, spatial heterogeneity in ferroptosis susceptibility, and the need for validated predictive biomarkers. By synthesizing these cutting-edge findings, we provide a framework that integrates cancer genetics, microenvironment metabolism, and immunology, distinguishing this review from previous summaries and highlighting actionable vulnerabilities for overcoming chemoresistance in ovarian cancer.  \nKeywords Ovarian cancer, Ferroptosis, Chemotherapy resistance, GPX4, PARP inhibitors, Compensatory threshold  \n*Correspondence: Shuqing Li[q1004239849@163.com](q1004239849@163.com)[ ](q1004239849@163.com)Zhiling Zhu [zhilingzhu888@126.com](zhilingzhu888@126.com)  \n1Obstetrics & Gynecology Hospital of Fudan University, Shanghai Key Laboratory of Reproduction and Development, Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai 200433, China  \n2Cancer Institute, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University,  \nShanghai 200032, China  \n© The Author(s) 2026, modified publication 2026. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creativecom](http://creativecom)[mons.org/licenses/by/4.0/](mons.org/licenses/by/4.0/.)[.](mons.org/licenses/by/4.0/.)  \nLi et al. Journal of Ovarian Research (2026) 19:220  \nIntroduction  \nOvarian cancer accounts for more deaths than any other gynecologic malignancy. According to GLOBOCAN 2022 estimates, approximately 324,000 women are diagnosed annually worldwide, with 207,000 succumbing to the disease [1]. Survival rates have stagnated","cbCaimJIFEUEPHDT","https://ap.wps.com/l/cbCaimJIFEUEPHDT","pdf",1639300,"English","# Abstract\n# Introduction","[{\"question\":\"What problem does the review focus on in ovarian cancer treatment?\",\"answer\":\"The review focuses on acquired platinum resistance, which accounts for most treatment failures and leads to relapse in advanced disease.\"},{\"question\":\"How is ferroptosis described, and why is it relevant to therapy resistance?\",\"answer\":\"Ferroptosis is an iron-dependent regulated cell death driven by lipid peroxidation. The review argues it creates a metabolic vulnerability that therapy-resistant cancers cannot fully evade.\"},{\"question\":\"Which ferroptosis-related mechanisms are analyzed in relation to chemotherapy resistance?\",\"answer\":\"The review examines the GPX4 antioxidant axis, polyunsaturated fatty acid biosynthesis, and iron homeostasis, and highlights findings such as BRCA1-dependent GPX4 regulation and NR1D2-mediated repression of FSP1.\"}]","Ferroptosis and chemotherapy resistance in ovarian cancer: molecular mechanismsand therapeutic opportunities | PDF",1790103175,25]