[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-382954-105":59,"doc-detail-382954-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","kdm4c-mediated-senescence-defense-is-a-targetable-vulnerability-in-gastric-cancer-harboring-tp53-mutations","KDM4C-mediated senescence defense is a targetable vulnerability in gastric cancer harboring TP53 mutations","","Gastric cancer patients with TP53 mutations show more aggressive, chemoresistant behavior, yet therapeutic vulnerabilities remain difficult to identify. This study explores epigenetic modulators as a route to trigger senescence, an approach supported by broader cancer therapy benefits and “one-two punch” trial evidence. QC6352, a selective KDM4C inhibitor, induces cellular senescence and combined treatment with the senolytic agent SSK1 eliminates TP53-mutant tumor cells.",{"@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":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/kdm4c-mediated-senescence-defense-is-a-targetable-vulnerability-in-gastric-cancer-harboring-tp53-mutations/382954/",{"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/kdm4c-mediated-senescence-defense-is-a-targetable-vulnerability-in-gastric-cancer-harboring-tp53-mutations/382954.png","ImageObject",300,407,{"name":92,"@type":93},"Grenda","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-22","2026-09-24",true,{"@type":102,"interactionType":103,"userInteractionCount":19},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"Why focus on TP53-mutant gastric cancer in this study?","Question",{"text":112,"@type":113},"The document states that gastric cancer patients harboring TP53 mutations have a more aggressive and chemoresistant phenotype, and progress in identifying vulnerabilities has been limited.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What is QC6352 and what did the study demonstrate?",{"text":117,"@type":113},"QC6352 is presented as a selective KDM4C inhibitor. It efficiently triggers cellular senescence in gastric cancer cells harboring TP53 mutations.",{"name":119,"@type":110,"acceptedAnswer":120},"How does the “one-two punch” therapy work according to the paper?",{"text":121,"@type":113},"The “one-two punch” consists of QC6352 followed by the senolytic agent SSK1. Together, they eliminate tumor cells harboring TP53 mutations.","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},382954,1791974220,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":19,"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},7971474921005,"https://ap-avatar.wpscdn.com/davatar_29158cc5080c5b710cf443261637dec0","Wang et al. Clinical Epigenetics (2023) 15:163 [https://doi.org/10.1186/s13148-023-01579-6](https://doi.org/10.1186/s13148-023-01579-6)  \nClinical Epigenetics  \n RESEARCH Open Access  \nKDM4C-mediated senescence defense is a targetable vulnerability in gastric cancer harboring TP53 mutations  \nKaiqing Wang1,2,3†, Zhicheng Gong2,3*†, Yanyan Chen2,3, Meimei Zhang4, Suzeng Wang1,2,3, Surui Yao2,3, Zhihui Liu2, Zhaohui Huang2,3* and Bojian Fei 1*  \nAbstract  \nBackground Gastric cancer patients harboring a TP53 mutation exhibit a more aggressive and chemoresistant phenotype. Unfortunately, efforts to identify the vulnerabilities to overcome these aggressive malignancies have made minimal progress in recent years. Therefore, there is an urgent need to explore the novel therapeutic strategies for this subclass. Histone methylation modulators are critical epigenetic targets for cancer therapies that help maintain the malignancies of cancers harboring TP53 mutations and senescence evasion. Triggering senescence is now considered to benefit multiple cancer therapies. Furthermore, senescence-based “one-two punch” therapy was validated in clinical trials. Therefore, we hypothesized that screening epigenetic modulators might help identify a novel vulnerability to trigger senescence in gastric cancer harboring TP53 mutations.  \nResults We developed a novel efficient approach to identify senescence inducers by sequentially treating cells with drug candidates and senolytic agents. Based on this, we demonstrated that QC6352 (a selective KDM4C inhibitor) efficiently triggered cellular senescence in gastric cancer harboring TP53 mutations. More importantly, the “onetwo punch’ therapy consisting of QC6352 and SSK1 eliminates tumor cells harboring TP53 mutations. This finding highlights a potential therapeutic strategy for the aggressive subgroup of gastric cancer. Besides, the functions of QC6352 were totally unknown. We demonstrated that QC6352 might possess far more powerful anti-tumor capacities compared to the traditional genotoxic drugs, 5-Fu and Oxaliplatin.  \nConclusions This initial investigation to identify a senescence inducer revealed that QC6352 triggers senescencein gastric cancer cells harboring TP53 mutations by regulating the SP1/CDK2 axis through suppressing KDM4C. QC6352 and senolytic agent-SSK1 represent a novel ‘one-two punch’ therapeutic strategy for the more malignant gastric cancer subtypes.  \n†Kaiqing Wang and Zhicheng Gong contributed equally to this work.  \n*Correspondence:  \nZhicheng Gong [9862021019@jiangnan.edu.cn](9862021019@jiangnan.edu.cn)[ ](9862021019@jiangnan.edu.cn)Zhaohui Huang [zhaohuihuang@jiangnan.edu.cn](zhaohuihuang@jiangnan.edu.cn)[ ](zhaohuihuang@jiangnan.edu.cn)Bojian Fei  \n[wx4yfbj@163.com](wx4yfbj@163.com)  \nFull list of author information is available at the end of the article  \n© The Author(s) 2023. 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/. The Creative Commons Public Domain Dedication waiver ()[. The Creative Commons Public Domain Dedication waiver (](http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ()[http://cr","cbCaipAi5qFjrgUA","https://ap.wps.com/l/cbCaipAi5qFjrgUA","pdf",6432364,13,"English","# Abstract\n## Background\n## Results\n## Conclusions\n# Highlights\n# Introduction","[{\"question\":\"Why focus on TP53-mutant gastric cancer in this study?\",\"answer\":\"The document states that gastric cancer patients harboring TP53 mutations have a more aggressive and chemoresistant phenotype, and progress in identifying vulnerabilities has been limited.\"},{\"question\":\"What is QC6352 and what did the study demonstrate?\",\"answer\":\"QC6352 is presented as a selective KDM4C inhibitor. It efficiently triggers cellular senescence in gastric cancer cells harboring TP53 mutations.\"},{\"question\":\"How does the “one-two punch” therapy work according to the paper?\",\"answer\":\"The “one-two punch” consists of QC6352 followed by the senolytic agent SSK1. Together, they eliminate tumor cells harboring TP53 mutations.\"}]","KDM4C-mediated senescence defense is a targetable vulnerability in gastric cancer harboring TP53 mutations | PDF",1790253219,33]