[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-326689-105":59,"doc-detail-326689-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","exploring-the-landscape-of-drug-resistance-in-gastrointestinal-cancer-immunotherapy-a-review","Exploring the landscape of drug resistance in gastrointestinal cancer immunotherapy - A review","","Gastrointestinal cancers represent a major global challenge due to high prevalence and mortality, with poor prognosis especially in advanced stages. Immunotherapy has advanced treatment by engaging the immune system through immune checkpoint inhibitors, cancer vaccines, and adoptive cell transfer, yielding sustained responses in some patients. However, efficacy in GI cancers remains limited because intrinsic and acquired drug resistance reduces benefit. The review analyzes key resistance mechanisms, including immune checkpoint alterations, immunosuppressive tumor microenvironment, genetic/epigenetic changes, and gut microbiome involvement. It also surveys strategies to enhance immunity, target the microenvironment, and explore ferroptosis induction while emphasizing the need for personalized approaches and further mechanistic research.",{"@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/exploring-the-landscape-of-drug-resistance-in-gastrointestinal-cancer-immunotherapy-a-review/326689/",{"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/exploring-the-landscape-of-drug-resistance-in-gastrointestinal-cancer-immunotherapy-a-review/326689.png","ImageObject",300,407,{"name":92,"@type":93},"Jiven","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-26","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":34},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What therapies does the review cover for gastrointestinal cancer immunotherapy?","Question",{"text":112,"@type":113},"It focuses on immune checkpoint inhibitors (ICIs), cancer vaccines, and adoptive cell transfer (ACT), summarizing their outcomes and limitations in GI cancers.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"Why is drug resistance a major obstacle in GI cancer immunotherapy?",{"text":117,"@type":113},"Drug resistance can be intrinsic or acquired, allowing cancer cells to adapt and continue growing and spreading despite immunotherapeutic interventions.",{"name":119,"@type":110,"acceptedAnswer":120},"Which mechanisms and factors contribute to drug resistance discussed in the review?",{"text":121,"@type":113},"The review highlights changes in immune checkpoints, the immunosuppressive tumor microenvironment, genetic/epigenetic alterations, and the gut microbiome as an emerging resistance factor.","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},326689,1791081187,{"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":34,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":29,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":144,"preview_page_count":4},1099513958607,"https://ap-avatar.wpscdn.com/avatar/100002390cf8733938c?x-image-process=image/resize,m_fixed,w_180,h_180&k=1778829742770036399","®  \n Narrative Review   \nExploring the landscape of drug resistance in gastrointestinal cancer immunotherapy A review  \nNan Yao, MDa , Wenqiang Li, MDa , Ning Duan, MDa , Guoshuai Xu, MDa , Guoyong Yu, PhDb , Jun Qu, PhDa ,*  \n\n| Abstract\u003Cbr>Gastrointestinal (GI) cancers pose a significant challenge due to high prevalence and mortality. While advancements in detection and conventional treatments have been made, prognosis often remains poor, particularly for advanced-stage cancers. Immunotherapy has emerged as a transformative approach, leveraging the body immune system against cancer, including immune checkpoint inhibitors (ICIs), cancer vaccines, and adoptive cell transfer. These modalities have shown promise, achieving sustained responsesand improved survival in some patients. However, their efficacy in GI cancers is less pronounced, hindered by drug resistance mechanisms that are either intrinsic or acquired over time. This review examines the latest understanding of immunotherapy in GI cancers, focusing on ICIs, cancer vaccines, and adoptive cell transfer, along with their associated outcomes and limitations. It delves into the mechanisms behind drug resistance, including alterations in immune checkpoints, the immunosuppressive tumor microenvironment, and genetic/epigenetic changes. The role of the gut microbiome is also considered as an emerging factor in resistance. To combat drug resistance, strategies such as enhancing immune response, targeting the tumor microenvironment, and modulating resistance mechanisms are explored. The review underscores the potential of ferroptosis induction as a novel approach. Looking forward, it highlights the need for personalized immunotherapies, understanding the influence of the gut microbiome, and further exploration of ferroptosis in overcoming resistance. While challenges persist, the continuous evolution in GI cancer immunotherapy research promises innovative treatments that could significantly improve patient outcomes. |\n| --- |\n| Abbreviations: ACT = adoptive cell transfer, GI = gastrointestinal, ICIs = immune checkpoint inhibitors, OS = overall survival. |\n| Keyword: cancer immunotherapy, drug resistance, ferroptosis, immune checkpoint blockade, tumor microenvironment |\n\n1. Introduction  \nGastrointestinal (GI) cancers, which assail the digestive tract, have a significant presence in the global cancer landscape due to their prevalence and mortality rates. [1] This group includes cancers of the esophagus, stomach, liver, pancreas, gallbladder, and colorectum. Despite advancements in early detection and treatments such as surgery, radiation, and chemotherapy, the prognosis remains poor for many, especially those diagnosed at advanced stages. [2,3] In recent times, immunotherapy has risen to the forefront of cancer treatments, offering hope for numerous cancer types, including GI cancers. [4] Immunotherapy harnesses the body immune system to detect and eliminate malignant cells. Its range of therapies includes immune checkpoint inhibitors (ICIs), cancer vaccines, and the innovative method of adoptive cell transfer (ACT) . [5–7] These treatments have yielded promising outcomes in various cancers, such as lung cancer,[8,9] breast cancer,[10] and melanoma,[11,12] resulting in sustained responses and enhanced survival for some patients. However, the effectiveness of  \nimmunotherapy for GI cancers has not been as pronounced, especially when compared to its notable successes in treating cancers like melanoma and lung cancer.[13] A significant challenge is the development of drug resistance, where cancer cells cleverly adapt, continuing to grow, and spread despite immunotherapeutic interventions. [14,15] This resistance can be present from the start of treatment (intrinsic resistance) or may develop as treatment progresses (acquired resistance) . [16] It’s crucial to understand the mechanisms of drug resistance in GI cancer immunotherapy. This understanding helps predict patient responses t","cbCaiiMiWkgAS8SS","https://ap.wps.com/l/cbCaiiMiWkgAS8SS","pdf",466732,"English","# Introduction\n## Immunotherapy in gastrointestinal cancer\n### Immune checkpoint inhibitors and GI cancers","[{\"question\":\"What therapies does the review cover for gastrointestinal cancer immunotherapy?\",\"answer\":\"It focuses on immune checkpoint inhibitors (ICIs), cancer vaccines, and adoptive cell transfer (ACT), summarizing their outcomes and limitations in GI cancers.\"},{\"question\":\"Why is drug resistance a major obstacle in GI cancer immunotherapy?\",\"answer\":\"Drug resistance can be intrinsic or acquired, allowing cancer cells to adapt and continue growing and spreading despite immunotherapeutic interventions.\"},{\"question\":\"Which mechanisms and factors contribute to drug resistance discussed in the review?\",\"answer\":\"The review highlights changes in immune checkpoints, the immunosuppressive tumor microenvironment, genetic/epigenetic alterations, and the gut microbiome as an emerging resistance factor.\"}]","Exploring the landscape of drug resistance in gastrointestinal cancer immunotherapy - A review | PDF",1789975092,15]