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This review contrasts the two systems for prognostic value across geographic populations, highlighting ACRG’s practicality for East Asia and TCGA’s strength for mechanistic discovery. It examines acquired resistance central to precision therapy, detailing anti-HER2 resistance and primary/secondary ICI resistance, immune-related adverse events, and pseudo-/hyperprogression.",{"@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/molecular-classification-and-precision-therapy-in-gastric-cancer-current-advances-and-future-perspectives/354640/",{"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/molecular-classification-and-precision-therapy-in-gastric-cancer-current-advances-and-future-perspectives/354640.png","ImageObject",300,407,{"name":92,"@type":93},"dhado","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-23","2026-09-22",true,{"@type":102,"interactionType":103,"userInteractionCount":24},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What are the main real-world obstacles to clinical translation of molecular classifications in gastric cancer?","Question",{"text":112,"@type":113},"Clinical translation is limited by high cost, tissue availability, standardization challenges, and intratumoral heterogeneity.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How do TCGA and ACRG differ in their prognostic utility and applicability?",{"text":117,"@type":113},"ACRG is described as more operable for East Asian populations, while TCGA better supports mechanistic exploration.",{"name":119,"@type":110,"acceptedAnswer":120},"What resistance issues are emphasized as core bottlenecks in precision therapy for gastric cancer?",{"text":121,"@type":113},"The review focuses on acquired resistance, including mechanisms of anti-HER2 resistance and primary/secondary resistance to immune checkpoint inhibitors.","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},354640,1790545331,{"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":24,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":56,"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},5909893218464,"https://ap-avatar.wpscdn.com/davatar_085a072bc5b1113ac321206ff7593b45","ONCOLOGY REPORTS 56: 174, 2026  \nMolecular classification and precision therapy in gastric cancer:  \nCurrent advances and future perspectives (Review)  \nSHUJING XIA 1,2 , XIUMEI ZHANG3 , LIZHONG TANG4,5 , ANQI LI 1,2 , JIANHAI CHEN 1,2 and ZHANG TAO6,7  \n1Department of Gastroenterology, Yancheng TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Yancheng, Jiangsu 224001, P.R. China; 2Department of Gastroenterology, Yancheng TCM Hospital, Yancheng, Jiangsu 224001, P.R. China; 3Department of Pathology, Affiliated Xinghua People's Hospital of Yangzhou University Medical College, Xinghua, Jiangsu 225700, P.R. China; 4Department of Pharmacy, Yancheng TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Yancheng, Jiangsu 224001, P.R. China; 5Department of Pharmacy, Yancheng TCM Hospital, Yancheng, Jiangsu 224001, P.R. China; 6Department of Respiratory Medicine, Yancheng TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Yancheng, Jiangsu 224001, P.R. China; 7Department of Respiratory Medicine, Yancheng TCM Hospital, Yancheng, Jiangsu 224001, P.R. China  \nReceived October 17, 2025; Accepted May 13, 2026  \nDOI: 10. 3892/or.2026.9180  \nAbstract. The emergence of molecular classifications for gastric cancer (GC), The Cancer Genome Atlas (TCGA) and Asian Cancer Research Group (ACRG), has advanced targeted and immunotherapies, but their clinical translation faces real‑world obstacles including high cost, tissue availability, standardization, and intratumoral heterogeneity. The present review critically compares the two classification systems regarding prognostic utility across geographic populations and boundary conflicts, noting that ACRG is more operable in East Asian populations whereas TCGA is better suited for mechanistic exploration. Focusing on acquired resistance as a core bottleneck in precision therapy, mechanisms underlying anti‑Human Epidermal Growth Factor Receptor 2 (HER2) resistance and primary/secondary resistance to immune checkpoint inhibitors (ICIs) were systematically dissected, while also addressing immune‑related adverse events and pseudo‑/hyperprogression . Moreover, non‑immune elements of the tumor microenvironment deserve attention: Cancer‑associated fibroblasts limit drug penetration and promote epithelial‑mesenchymal transition through phys‑ ical barriers and paracrine signaling; metabolic reprogramming (high glycolysis and glutamine addiction) impairs chemotherapy and ICI efficacy via an acidic microenvironment and metabolic competition. Finally, multi‑target combination strategies are envisioned based on pathway redundancy, along with liquid biopsy‑driven dynamic adaptive therapy and single‑cell/spatial  \nCorrespondence to: Professor Zhang Tao, Department of Respiratory Medicine, Yancheng TCM Hospital Affiliated to Nanjing University of Chinese Medicine, 53 Renmin Road, Yancheng, Jiangsu 224001, P.R. China  \nE‑mail: [taozhang1978@163.com](taozhang1978@163.com)  \nKey words: gastric cancer, molecular classification, precision therapy, targeted therapy, immunotherapy  \nmulti‑omics integration for precise microenvironment interven‑ tion. The present review aims to offer a systematic reference for moving GC precision therapy from static subtyping toward dynamic, multi‑dimensional integration.  \nContents  \n1. Introduction  \n2. Molecular classification of GC  \n3. Precision therapy based on molecular subtypes  \n4. Future outlook: pathway redundancy‑informed combi‑ nation therapies and dynamically adaptive treatment strategies in GC  \n5. Conclusion  \n1. Introduction  \nGastric cancer (GC) continues to pose a significant global health challenge, with GLOBOCAN 2022 data indicating~1 .09 million new cases and 768,000 annual deaths world‑ wide (1‑3) . It remains the fifth most commonly diagnosed cancer across populations and ranks third in cancer‑related mortality, following only lung and colorectal cancers (4,5) . The prognosis for patients remains largely unfavorable, as age‑s","cbCaicAQQSpBRTuA","https://ap.wps.com/l/cbCaicAQQSpBRTuA","pdf",3238871,"English","# 1. Introduction\n# 2. Molecular classification of GC\n# 3. Precision therapy based on molecular subtypes\n# 4. Future outlook: pathway redundancy-informed combination therapies and dynamically adaptive treatment strategies in GC\n# 5. Conclusion","[{\"question\":\"What are the main real-world obstacles to clinical translation of molecular classifications in gastric cancer?\",\"answer\":\"Clinical translation is limited by high cost, tissue availability, standardization challenges, and intratumoral heterogeneity.\"},{\"question\":\"How do TCGA and ACRG differ in their prognostic utility and applicability?\",\"answer\":\"ACRG is described as more operable for East Asian populations, while TCGA better supports mechanistic exploration.\"},{\"question\":\"What resistance issues are emphasized as core bottlenecks in precision therapy for gastric cancer?\",\"answer\":\"The review focuses on acquired resistance, including mechanisms of anti-HER2 resistance and primary/secondary resistance to immune checkpoint inhibitors.\"}]","Molecular classification and precision therapy in gastric cancer - Current advances and future perspectives | PDF",1790112709,48]