[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-331956-105":59,"doc-detail-331956-en":131},{"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":124,"head_meta":126,"extra_data":128,"updated_unix":130},105,"en","cancer-associated-fibroblasts-protagonists-of-the-tumor-microenvironment-in-gastric-cancer","Cancer-associated fibroblasts: protagonists of the tumor microenvironment in gastric cancer","","Enhanced knowledge of the interaction between cancer cells and their environment highlights how the tumor microenvironment drives tumor progression and chemoresistance. Cancer-associated fibroblasts (CAFs) function as key orchestrators that promote metastasis, stemness, and chemoresistance, while weakening anti-cancer immune responses. Gastric cancer remains highly aggressive and refractory to therapies, with CAFs strongly linked to an unfavorable tumor immune microenvironment and poor prognosis. Targeting CAFs may help overcome resistance to conventional chemotherapy, molecular-targeted therapy, and immunotherapy, though CAF heterogeneity complicates strategy development. This review synthesizes current knowledge, focusing on how CAFs induce aggressiveness and therapy resistance in gastric cancer and outlining potential therapeutic approaches that inhibit CAF inducers and markers.",{"@graph":69,"@context":123},[70,84,106],{"@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/cancer-associated-fibroblasts-protagonists-of-the-tumor-microenvironment-in-gastric-cancer/331956/",{"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/cancer-associated-fibroblasts-protagonists-of-the-tumor-microenvironment-in-gastric-cancer/331956.png","ImageObject",300,407,{"name":92,"@type":93},"Lucas Martin","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-29","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",11,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"What roles do cancer-associated fibroblasts (CAFs) play in gastric cancer?","Question",{"text":113,"@type":114},"CAFs promote metastasis, stemness, and chemoresistance, while attenuating anti-cancer immune responses. In gastric cancer, they contribute to an unfavorable tumor immune microenvironment and poor prognosis.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"Why is the tumor microenvironment (TME) important for cancer progression and treatment resistance?",{"text":118,"@type":114},"The TME provides a supportive “fertile soil” for cancer cell proliferation. Through cellular and non-cellular interactions, it enables invasion, immune evasion, chemotherapy resistance, and angiogenesis.",{"name":120,"@type":111,"acceptedAnswer":121},"What challenges arise when developing CAF-targeting therapies?",{"text":122,"@type":114},"CAF heterogeneity complicates the development of targeting approaches. Even though single-cell sequencing has begun to dissect this heterogeneity, key questions about CAF subtype functions remain.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},331956,1790520249,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":140,"language":141,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":67,"update_tm":145,"read_time":146},8796095360427,"https://ap-avatar.wpscdn.com/davatar_994ba38a5ba835b3df7d355c54d3ed8d","TYPE Review  \nPUBLISHED 18 March 2024  \nDOI 10.3389/fmolb.2024.1340124  \nOPEN ACCESS  \nEDITED BY  \nXuezhen Zeng,  \nThe First Affiliated Hospital of Sun Yat-sen University, China  \nREVIEWED BY  \nSurjendu Maity,  \nTerasaki Institute for Biomedical Innovation, United States  \nTapahsama Banerjee,  \nUniversity of Colorado, United States  \n*CORRESPONDENCE  \nGulnihal Ozcan,  \n [guozcan@ku.edu.tr](guozcan@ku.edu.tr)  \nRECEIVED 17 November 2023  \nACCEPTED 31 January 2024  \nPUBLISHED 18 March 2024  \nCITATION  \nOzmen E, Demir TD and Ozcan G (2024), Cancer-associated fibroblasts: protagonists of the tumor microenvironment in gastric cancer. Front. Mol. Biosci. 11:1340124 .  \ndoi: 10.3389/fmolb.2024.1340124  \nCOPYRIGHT  \n© 2024 Ozmen, Demir and Ozcan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.  \nCancer-associated fibroblasts: protagonists of the tumor microenvironment in  \ngastric cancer  \nEce Ozmen 1, Tevriz Dilan Demir 2 and Gulnihal Ozcan 2,3*  \n1Koç University Graduate School of Health Sciences, Istanbul, Türkiye, 2Koç University Research Center for Translational Medicine (KUTTAM), Istanbul, Türkiye, 3Department of Medical Pharmacology, Koç University School of Medicine, Istanbul, Türkiye  \nEnhanced knowledge of the interaction of cancer cells with their environment elucidated the critical role of tumor microenvironment in tumor progression and chemoresistance. Cancer-associated fibroblasts act as the protagonists of the tumor microenvironment, fostering the metastasis, stemness, and chemoresistance of cancer cells and attenuating the anti-cancer immune responses. Gastric cancer is one of the most aggressive cancers in the clinic, refractory to anti-cancer therapies. Growing evidence indicates that cancerassociated fibroblasts are the most prominent risk factors for a poor tumor immune microenvironment and dismal prognosis in gastric cancer. Therefore, targeting cancer-associated fibroblasts may be central to surpassing resistance to conventional chemotherapeutics, molecular-targeted agents, and immunotherapies, improving survival in gastric cancer. However, the heterogeneity in cancer-associated fibroblasts may complicate the development of cancer-associated fibroblast targeting approaches. Although single-cell sequencing studies started dissecting the heterogeneity of cancerassociated fibroblasts, the research community should still answer these questions: “What makes a cancer-associated fibroblast protumorigenic?”;“How do the intracellular signaling and the secretome of different cancerassociated fibroblast subpopulations differ from each other?”; and “Which cancer-associated fibroblast subtypes predominate specific cancer types?”. Unveiling these questions can pave the way for discovering efficient cancerassociated fibroblast targeting strategies. Here, we review current knowledge and perspectives on these questions, focusing on how CAFs induce aggressiveness and therapy resistance in gastric cancer. We also review potential therapeutic approaches to prevent the development and activation of cancer-associated fibroblasts via inhibition of CAF inducers and CAF markers in cancer.  \nKEYWORDS  \ncancer-associated fibroblasts, tumor microenvironment, gastric cancer, chemoresistance, stemness, metastasis  \n1 Introduction  \nCancer is a highly dynamic and complex disease that evolves through the dynamic interaction of cancer cells with the tumor microenvironment (TME) . The TME acts as a fertile soil to support the proliferation of cancer cells (de Visser and Joyce, 2023) . To further feed this fertile soil, cancer cells secrete soluble factors like chemokin","cbCaibm1AyOKb6Qr","https://ap.wps.com/l/cbCaibm1AyOKb6Qr","pdf",1644666,18,"English","# Introduction\n## Tumor microenvironment as a dynamic system\n## Cellular components and CAF origins\n## Extracellular matrix and signaling\n# CAFs in gastric cancer\n## CAF roles in aggressiveness and therapy resistance\n## CAF-driven immune evasion\n## CAF-driven chemoresistance and stemness\n# Key research questions and heterogeneity\n## Intracellular signaling differences among CAF subtypes\n## Secretome differences among CAF subpopulations\n## Dominant CAF subtypes across cancer types\n# Therapeutic targeting strategies\n## Inhibiting CAF inducers\n## Targeting CAF markers","[{\"question\":\"What roles do cancer-associated fibroblasts (CAFs) play in gastric cancer?\",\"answer\":\"CAFs promote metastasis, stemness, and chemoresistance, while attenuating anti-cancer immune responses. In gastric cancer, they contribute to an unfavorable tumor immune microenvironment and poor prognosis.\"},{\"question\":\"Why is the tumor microenvironment (TME) important for cancer progression and treatment resistance?\",\"answer\":\"The TME provides a supportive “fertile soil” for cancer cell proliferation. Through cellular and non-cellular interactions, it enables invasion, immune evasion, chemotherapy resistance, and angiogenesis.\"},{\"question\":\"What challenges arise when developing CAF-targeting therapies?\",\"answer\":\"CAF heterogeneity complicates the development of targeting approaches. Even though single-cell sequencing has begun to dissect this heterogeneity, key questions about CAF subtype functions remain.\"}]","Cancer-associated fibroblasts: protagonists of the tumor microenvironment in gastric cancer | PDF",1789995981,45]