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Tumor stroma composed of cancer-associated fibroblasts, immune cells, and vascular components shows marked spatial and temporal diversity. Stromal elements drive reciprocal crosstalk with cancer cells, promoting proliferation, invasion, and metastasis, while enabling resistance to chemotherapy, targeted therapy, and immunotherapy. The review summarizes mechanisms of TME evolution and highlights therapeutic implications and challenges.",{"@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/role-and-value-of-the-tumor-microenvironment-in-the-progression-and-treatment-resistance-of-gastric-cancer-review/332836/",{"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/role-and-value-of-the-tumor-microenvironment-in-the-progression-and-treatment-resistance-of-gastric-cancer-review/332836.png","ImageObject",300,407,{"name":92,"@type":93},"Evangeline","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-23","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":44},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What role does the tumor microenvironment play in gastric cancer progression?","Question",{"text":112,"@type":113},"The TME actively coordinates communication networks and released elements that shape cancer cell behavior and therapy response, driving progression through dynamic interactions.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"Which TME components are highlighted as influencing treatment resistance?",{"text":117,"@type":113},"The review emphasizes tumor stroma including cancer-associated fibroblasts, immune cells, vascular components, and the extracellular matrix, which together facilitate resistance to chemotherapy, targeted treatments, and immunotherapy.",{"name":119,"@type":110,"acceptedAnswer":120},"How do stromal elements interact with cancer cells?",{"text":121,"@type":113},"Stromal elements engage in dynamic crosstalk that supports proliferative, invasive, and metastatic potential while enabling adaptive behavior toward therapy.","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},332836,1790192947,{"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":44,"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":36,"preview_page_count":4},13056703019662,"https://ap-avatar.wpscdn.com/avatar/be000253a8e92610077?_k=1778726343310543188","ONCOLOGY REPORTS 53: 14, 2025  \nRole and value of the tumor microenvironment in the progression and treatment resistance of gastric cancer (Review)  \nHENGYUN 1* , FANGDE DONG 1* , XIAOQIN WEI2 , XINYONG YAN3 ,  \nRONGLONG ZHANG 1 , XIUYU ZHANG4 and YULIN WANG 1  \n1Department of General Surgery, The Third Affiliated Hospital of Gansu University of Traditional Chinese Medicine, Baiyin, Gansu 730900, 2 3  \nP.R. China; Department of Pain, The Second People's Hospital of Baiyin, Baiyin, Gansu 730900, P.R. China; Department of Proctology, The Third Affiliated Hospital of Gansu University of Traditional Chinese Medicine, Baiyin, Gansu 730900, P.R. China; 4Department of Gastroenterology, The Third Affiliated Hospital of Gansu University of Traditional Chinese Medicine, Baiyin, Gansu 730900, P.R. China  \nReceived August 8, 2024; Accepted October 8, 2024  \nDOI: 10. 3892/or.2024.8847  \nAbstract. Gastric cancer (GC) is characterized by a complex and heterogeneous tumor microenvironment (TME) that significantly influences disease progression and treatment outcomes. The tumor stroma, which is composed of a variety of cell types such as cancer‑associated fibroblasts, immune cells and vascular components, displays significant spatial and temporal diversity. These stromal elements engage in dynamic  \nCorrespondence to: Dr Xiuyu Zhang, Department of Gastroenterology, The Third Affiliated Hospital of Gansu University of Traditional Chinese Medicine, 222 Silong Road, Baiyin, Gansu 730900, P.R. China  \nE‑mail: [540233457@qq.com](540233457@qq.com)  \nProfessor Yulin Wang, Department of General Surgery, The Third Affiliated Hospital of Gansu University of Traditional Chinese Medicine, 222 Silong Road, Baiyin, Gansu 730900, P.R. China  \nE‑mail: [279113042@qq.com](279113042@qq.com)  \n*Contributed equally  \nAbbreviations: GC, gastric cancer; TME, tumor microenvironment; CAFs, cancer‑associated fibroblasts; ECM, extracellular matrix; TGF‑β, transforming growth factor β; PDGF, platelet‑derived growth factor; FGF, fibroblast growth factor; TAMs, tumor‑associated macrophages; Tregs, regulatory T cells; MDSCs, myeloid‑derived suppressor cells; VEGF, vascular endothelial growth factor; MMPs, matrix metalloproteinases; EMT, epithelial‑mesenchymal transition; HGF, hepatocyte growth factor; IL‑6, interleukin‑6; TNF‑α , tumor necrosis factor‑α; LOX, lysyl oxidase; HIF, hypoxia‑inducible factor; FAP, fibroblast activation protein; TECs, tumor‑associated endothelial cells; IL‑8, interleukin‑8; NGF, nerve growth factor; BDNF, brain‑derived neurotrophic factor; NK‑1R, neurokinin‑1 receptor; Trk, tropomyosin receptor kinase; NKs, natural killer cells; PD‑1, programmed cell death protein 1; IL‑10, interleukin‑10; CSCs, cancer stem cells  \nKey words: gastric cancer, tumor microenvironment, cancer‑associated fibroblasts, extracellular matrix, immune cell, therapeutic resistance  \ncrosstalk with cancer cells, shaping their proliferative, invasive and metastatic potential. Furthermore, the TMEis instrumental in facilitating resistance to traditional chemotherapy, specific treatments and immunotherapy strategies. Understanding the underlying mechanisms by which the GC microenvironment evolves and supports tumor growth and therapeutic resistance is critical for developing effective treatment strategies. The present review explores the latest progress in understanding the intricate interactions between cancer cells and their imme‑ diate environment in GC, highlighting the implications for disease pathogenesis and therapeutic interventions.  \nContents  \n1. Introduction  \n2. Composition and heterogeneity of TME in GC  \n3. Influence of TME evolution on GC progression  \n4. Mechanism of TME promoting GC resistance  \n5. Therapeutic methods of reducing GC resistance through TME effect  \n6. Outlook and challenges  \n7. Conclusion  \n1. Introduction  \nThe complexity and heterogeneity of gastric cancer (GC) pres‑ ents substantial difficulties in disease control and treatment (1) . Even wi","cbCaifxbpGTjAM38","https://ap.wps.com/l/cbCaifxbpGTjAM38","pdf",3114122,16,"English","# Introduction\n# Composition and heterogeneity of TME in GC\n# Influence of TME evolution on GC progression\n# Mechanism of TME promoting GC resistance\n# Therapeutic methods of reducing GC resistance through TME effect\n# Outlook and challenges\n# Conclusion","[{\"question\":\"What role does the tumor microenvironment play in gastric cancer progression?\",\"answer\":\"The TME actively coordinates communication networks and released elements that shape cancer cell behavior and therapy response, driving progression through dynamic interactions.\"},{\"question\":\"Which TME components are highlighted as influencing treatment resistance?\",\"answer\":\"The review emphasizes tumor stroma including cancer-associated fibroblasts, immune cells, vascular components, and the extracellular matrix, which together facilitate resistance to chemotherapy, targeted treatments, and immunotherapy.\"},{\"question\":\"How do stromal elements interact with cancer cells?\",\"answer\":\"Stromal elements engage in dynamic crosstalk that supports proliferative, invasive, and metastatic potential while enabling adaptive behavior toward therapy.\"}]","Role and value of the tumor microenvironment in the progression and treatment resistance of gastric cancer - Review | PDF",1789999698]