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This clinical urgency has driven the adoption of advanced therapies, including molecularly targeted therapies and immunotherapeutic strategies. Human epidermal growth factor receptor 2 (HER2)-directed agents, including trastuzumab, trastuzumab deruxtecan (T-DXd), and disitamab vedotin (RC48), have demonstrated significant survival benefits in HER2-positive cohorts, though intratumoral heterogeneity frequently underlies acquired resistance. Antiangiogenic therapies targeting the vascular endothelial growth factor receptor, exemplified by ramucirumab, remain a cornerstone of advanced GC management. Concurrently, immune checkpoint inhibitors against programmed cell death protein 1 and programmed cell death-ligand 1 have expanded therapeutic options by potentiating endogenous antitumor immunity, albeit with variable efficacy across molecular subtypes. Emerging immunotherapies\u2014such as adoptive cell therapies (e.g., chimeric antigen receptor T-cells), tumor-associated antigen vaccines, immunomodulatory agents, and genetically engineered oncolytic viruses\u2014show promising preclinical and early phase clinical activity. Critical to optimizing these advances is a systems-level understanding of the tumor-immune microenvironment, which dynamically regulates therapeutic response and immune evasion. Future progress hinges on three pillars: (1) biomarker-driven personalization of treatment regimens, (2) combinatorial strategies to overcome primary and adaptive resistance mechanisms, and (3) translational integration of multi-omics insights into therapeutic development. Addressing these priorities through mechanistic investigations and innovative trial designs will be essential to achieving durable clinical responses and improving survival outcomes in this heterogeneous malignancy.<\/jats:p>","DOI":"10.1177\/10815589251348919","type":"journal-article","created":{"date-parts":[[2025,5,31]],"date-time":"2025-05-31T01:36:22Z","timestamp":1748655382000},"page":"673-684","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":4,"title":["Advanced therapies for stomach cancer"],"prefix":"10.1177","volume":"73","author":[{"given":"Dong","family":"Luo","sequence":"first","affiliation":[{"name":"Center of Structural Heart Disease, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunmei","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Cultural Heritage and Information Management, Shanghai University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4225-9200","authenticated-orcid":false,"given":"Lei","family":"Huang","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Immunity and Inflammation, Changhai Clinical Research Unit, The First Affiliated Hospital of Naval Medical University\/Changhai Hospital, Naval Medical University, Shanghai, China"},{"name":"Department of Gastroenterology, National Clinical Research Center for Digestive Diseases, The First Affiliated Hospital of Naval Medical University\/Changhai Hospital, Naval Medical University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,7,12]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21834"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamasurg.2022.0182"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/abbs\/gmz141"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(10)61121-X"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-021-00492-2"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2021.0275"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/35052073"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(18)30481-9"},{"issue":"1","key":"e_1_3_3_10_2","first-page":"38","article-title":"Pertuzumab in combination with trastuzumab and chemotherapy for Chinese patients with HER2-positive metastatic gastric or gastroesophageal junction cancer: a subpopulation analysis of the JACOB trial","volume":"39","author":"Liu T","year":"2019","unstructured":"Liu T, Qin Y, Li J, et al. Pertuzumab in combination with trastuzumab and chemotherapy for Chinese patients with HER2-positive metastatic gastric or gastroesophageal junction cancer: a subpopulation analysis of the JACOB trial. 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