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This review examines how inflammatory pathways and epigenetic alterations jointly promote progression and chemo-resistance, supported by a 2000–2025 literature search and critical analysis of 593 peer-reviewed studies. It highlights anti-inflammatory and epigenetic-targeting combination strategies and calls for further clinical validation.",{"@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/inflammatory-milieu-and-role-of-epigenetic-modifications-in-high-grade-serous-ovarian-cancer/352590/",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/inflammatory-milieu-and-role-of-epigenetic-modifications-in-high-grade-serous-ovarian-cancer/352590.png","ImageObject",300,407,{"name":42,"@type":43},"Rhys","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-29","2026-09-22",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},"Why does HGSOC relapse so often despite initial treatment?","Question",{"text":63,"@type":64},"HGSOC relapse is largely linked to therapeutic resistance and adaptive chemoresistance processes, including tumor microenvironment-driven immune evasion and epigenetic reprogramming.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"What role does chronic inflammation in the tumor microenvironment play?",{"text":68,"@type":64},"Chronic inflammation in the tumor microenvironment supports tumor proliferation, immune suppression, epithelial–mesenchymal transition, and metastasis through cytokines, interferons, and chemokines.",{"name":70,"@type":61,"acceptedAnswer":71},"Which epigenetic mechanisms are highlighted as contributing to HGSOC plasticity and treatment failure?",{"text":72,"@type":64},"The review highlights DNA methylation, histone modifications, miRNA, and lncRNA as mechanisms that drive tumor plasticity and contribute to treatment failure.","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},352590,1790356517,{"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},687207024643,"https://ap-avatar.wpscdn.com/davatar_3d24733baf745e90a7e4bdd5f77d97b2","Pradhan et al. Clinical Epigenetics (2026) 18:47 [https://doi.org/10.1186/s13148-026-02080-6](https://doi.org/10.1186/s13148-026-02080-6)  \nClinical Epigenetics  \nREVIEW Open Access  \nInflammatory milieu and role of epigenetic modifications in high-grade serous ovarian cancer  \nSatarupa Pradhan 1, Shama Prasada Kabekkodu2, Sangavi Eswaran2, Naveena A. N. Kumar3, Dinesh Upadhya4, Sanjiban Chakrabarty5 and Vasudha Devi6*  \nAbstract  \nHigh-grade serous ovarian cancer (HGSOC) is often diagnosed at advanced stages (III/IV), with approximately 80% of patients experiencing relapse due to therapeutic resistance. The disease progression is largely influenced by a dynamic tumor microenvironment (TME), which is marked by sustained inflammation, immune evasion, and epigenetic reprogramming. This review investigates the dual role of inflammatory pathways and epigenetic alterations in driving HGSOC progression and chemo-resistance. A comprehensive literature search of articles from 2000 to 2025 was conducted across PubMed, Google Scholar, and Research Rabbit using search terms including“HGSOC,” “epigenetics,” “inflammation,” and “chemoresistance.” Of 1,166 identified publications, 593 peer-reviewed studies comprising original research, clinical trials, meta-analyses, and reviews were critically analyzed. Findings reveal that chronic inflammation in the TME enhances tumor proliferation, immune suppression, epithelialmesenchymal transition, and metastasis through cytokines, interferons, and chemokines. Epigenetic mechanisms such as DNA methylation, histone modifications, miRNA and lncRNA contribute to tumor plasticity and treatment failure. Emerging therapies, including histone deacetylase inhibitors, DNA methyltransferase inhibitors, and immune checkpoint inhibitors, anti-inflammatory drugs demonstrate potential in overcoming resistance when used in combination. Integrative treatment strategies that target both inflammatory signaling and epigenetic dysregulation offer a promising avenue for improving patient outcomes. Further clinical exploration of such combination therapies is warranted to address the urgent need for effective interventions in HGSOC.  \nKeywords HGSOC, Chronic inflammation, Inflammatory mediators, Epigenetics, Chemoresistance  \n*Correspondence:  \nVasudha Devi  \n[vasudha.devi@manipal.edu](vasudha.devi@manipal.edu)  \n1Department of Pharmacology, Kasturba Medical College, Manipal Academy of Higher Education, Manipal 576104, India  \n2Department of Cell and Molecular Biology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal 576104, India  \n3Department of Surgical Oncology, Kasturba Medical College, Manipal Academy of Higher Education, Manipal 576104, India  \n4Centre for Molecular Neurosciences, Kasturba Medical College, Manipal Academy of Higher Education, Manipal 576104, India  \n5Department of Public Health Genomics, Manipal School of Life Sciences, Manipal 576104, India  \n6Division of Pharmacology, Department of Basic Medical Sciences, Manipal Academy of Higher Education, Manipal 576104, India  \n© The Author(s) 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://creativecommons.org/licenses/by/4.0/](http://creativecommons.org/licenses/by/4.0/.)[","cbCaiab3w4RBvdam","https://ap.wps.com/l/cbCaiab3w4RBvdam","pdf",5073458,26,"English","# Abstract\n## Background","[{\"question\":\"Why does HGSOC relapse so often despite initial treatment?\",\"answer\":\"HGSOC relapse is largely linked to therapeutic resistance and adaptive chemoresistance processes, including tumor microenvironment-driven immune evasion and epigenetic reprogramming.\"},{\"question\":\"What role does chronic inflammation in the tumor microenvironment play?\",\"answer\":\"Chronic inflammation in the tumor microenvironment supports tumor proliferation, immune suppression, epithelial–mesenchymal transition, and metastasis through cytokines, interferons, and chemokines.\"},{\"question\":\"Which epigenetic mechanisms are highlighted as contributing to HGSOC plasticity and treatment failure?\",\"answer\":\"The review highlights DNA methylation, histone modifications, miRNA, and lncRNA as mechanisms that drive tumor plasticity and contribute to treatment failure.\"}]","Inflammatory milieu and role of epigenetic modifications in high-grade serous ovarian cancer | PDF",1790100369,66]