[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-356554-105":59,"doc-detail-356554-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","claudin182-promote-gastric-cancer-proliferation-by-activating-mcm25","Claudin18.2 promote gastric cancer proliferation by activating MCM2/5","","Pooled analysis of the SPOTLIGHT and GLOW phase III trials evaluates zolbetuximab plus chemotherapy in 1072 locally advanced or metastatic CLDN18.2-positive, HER2-negative GC/GEJ adenocarcinoma patients, showing significantly improved progression-free survival versus placebo (HR 0.72). Subgroup benefits emerge in Asian patients, gastric cancer, and intestinal-type tumors. In 92 GC patients, CLDN18.2 positivity correlates with lymph node metastasis, advanced stages (III–IV), and worse overall survival. Experimental CLDN18.2 knockdown suppresses tumor growth in vitro and in vivo via down-regulating MCM2 and MCM5 and reducing ERK/CDK/MCM2 phosphorylation, supporting CLDN18.2-targeted combination strategies.",{"@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/claudin182-promote-gastric-cancer-proliferation-by-activating-mcm25/356554/",{"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/claudin182-promote-gastric-cancer-proliferation-by-activating-mcm25/356554.png","ImageObject",300,407,{"name":92,"@type":93},"Jake","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-09-27","2026-09-23",true,{"@type":102,"interactionType":103,"userInteractionCount":81},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What does the pooled SPOTLIGHT and GLOW analysis show about zolbetuximab plus chemotherapy?","Question",{"text":112,"@type":113},"It significantly improves progression-free survival compared with placebo in CLDN18.2-positive, HER2-negative advanced or metastatic GC/GEJ adenocarcinoma patients.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How is CLDN18.2 linked to clinical outcomes in the 92-patient gastric cancer cohort?",{"text":117,"@type":113},"CLDN18.2 positivity associates with lymph node metastasis, advanced stages (III–IV), and shorter overall survival.",{"name":119,"@type":110,"acceptedAnswer":120},"What molecular effects are observed after CLDN18.2 knockdown in gastric cancer models?",{"text":121,"@type":113},"CLDN18.2 knockdown inhibits tumor growth and down-regulates MCM proteins, particularly MCM2 and MCM5, while decreasing phosphorylation of ERK, CDK, and MCM2.","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},356554,1790479184,{"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":81,"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},962084928904,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","[www. nature.com/scientificreports](www. nature.com/scientificreports)  \nOPEN  \nClaudin18.2 promote gastric cancer proliferation by activating MCM2/5  \nBowen Zheng1,2,3,8, Miao Fu1,8, Fanzhuoran Lou1,8, Yuting He1, Lingying Zhao4, Xintian Huang1, Xiaowen Xie1, Weijuan Tan1, Quan Chen1, Wenqing Zhang1, Yongxiang Hong1,7, Kaiyi Rong1, Yuyan Lu1, Ping Zhan1, Jingke Tu1, Huibo Shi5􀀍, Tianhui Hu1,3,6􀀍 & Li Xiao1􀀍  \nPooled analysis of the SPOTLIGHT and GLOW phase III trials, involving 1072 patients with locally advanced or metastatic gastric/gastroesophageal junction (GC/GEJ) adenocarcinoma positive for claudin18.2 (CLDN18.2) and negative for HER2, showed that zolbetuximab combined with chemotherapy significantly improved progression-free survival (PFS) compared to placebo (HR = 0.72; 95% CI, 0.61–0.84). Subgroup analyses revealed better outcomes in Asian patients, those with gastric cancer, and those with intestinal-type GC. In a cohort of 92 GC patients (immunohistochemical detection based on a CLDN18.2 subtype-specific antibody), CLDN18.2 positivity was associated with lymph node metastasis, advanced cancer stages (III–IV), and shorter overall survival (OS) (HR = 1.728; 95% CI, 1.003–2.977; P = 0.0404). In our study, knockdown ofCLDN18.2 inhibited tumor growth in vivo and in vitro. Additionally, CLDN18.2 knockdown down-regulated minichromosome maintenance (MCM) proteins, particularly MCM2 and MCM5, and decreased phosphorylation of ERK, CDK, and MCM2 in GC cells. These findings provide a theoretical basis for the future selection of advantageous populations for CLDN18.2-targeted therapy and combination therapy strategies.  \nKeywords CLDN18.2, Gastric cancer, MCM, RTK/MAPK, Proliferation  \nAbbreviations  \nGC Gastric cancer  \nGEJC Gastroesophageal junction cancer  \nCLDN18 .2 Claudin18 .2  \nHER2 Human epithelial growth factor receptor 2 PFS Progression-free survival  \nOS Overall survival  \nKM Kaplan-Meier  \nHR Hazard ratio  \nCIs Confidence intervals  \nGastric cancer (GC) ranks fourth in cancer-related mortality globally, representing one of the most formidable challenges in oncology1. Current treatment for advanced gastric cancer is stratified based on microsatellite instability (MSI) and human epidermal growth factor receptor 2 (HER2) status. For patients with MSI-high (MSI-H) tumors, clinical studies have shown significant benefit from PD-1 inhibitors, either as monotherapy2 orin combination with CTLA-4 inhibitor3. For HER2-positive patients, the KEYNOTE-811 study4 has established a standard regimen combining chemotherapy, immunotherapy, and anti-HER2 targeted therapy. For HER2-negative patients, trials including ATTRACTION-45, CheckMate-6494, COMPASSION-046, KEYNOTE-0627, KEYNOTE-8598, ORIENT-169 and RATIONALE-30510 have made immune checkpoint inhibitor (ICI) plus  \n1Department of Oncology, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361004, Fujian, China. 2Xiamen Key Laboratory for Tumor Metastasis, Cancer Research Center, School of Medicine, Xiamen University, Xiamen 361004, Fujian, China. 3National Institute for Data Science in Health and Medicine, Xiamen University, Xiamen 361102, Fujian, China. 4Department of Laboratory Medicine, Shenzhen Children’s Hospital, Shenzhen 518038, Guangdong, China. 5Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China.  \n6Shenzhen Research Institute of Xiamen University, Shenzhen 518057, Guangdong, China. 7The Graduate School of Fujian Medical University, Fujian Medical University, Fuzhou 350122, Fujian, China. 8Bowen Zheng, Miao Fu and Fanzhuoran Lou contributed equally to this work. 􀀍 email: [jimshihuibo@163.com](jimshihuibo@163.com); [thu@xmu.edu.cn](thu@xmu.edu.cn); [xlshb0826@xmu.edu.cn](xlshb0826@xmu.edu.cn)  \n[www. nature.com/scientificreports/](www. nature.com/scientificreports/)  \nchemotherapy the standard first-line treatment. Although HER2-targeted","cbCaiolCFGe7DWby","https://ap.wps.com/l/cbCaiolCFGe7DWby","pdf",7747894,14,"English","# Introduction\n## Treatment landscape for advanced gastric cancer\n## CLDN18.2 as a therapeutic target\n## Claudin biology and isoforms (CLDN18.1 vs CLDN18.2)\n## Evidence from SPOTLIGHT and GLOW trials","[{\"question\":\"What does the pooled SPOTLIGHT and GLOW analysis show about zolbetuximab plus chemotherapy?\",\"answer\":\"It significantly improves progression-free survival compared with placebo in CLDN18.2-positive, HER2-negative advanced or metastatic GC/GEJ adenocarcinoma patients.\"},{\"question\":\"How is CLDN18.2 linked to clinical outcomes in the 92-patient gastric cancer cohort?\",\"answer\":\"CLDN18.2 positivity associates with lymph node metastasis, advanced stages (III–IV), and shorter overall survival.\"},{\"question\":\"What molecular effects are observed after CLDN18.2 knockdown in gastric cancer models?\",\"answer\":\"CLDN18.2 knockdown inhibits tumor growth and down-regulates MCM proteins, particularly MCM2 and MCM5, while decreasing phosphorylation of ERK, CDK, and MCM2.\"}]","Claudin18.2 promote gastric cancer proliferation by activating MCM2/5 | PDF",1790125935,35]