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Research suggests that targeted therapy and immunotherapy may become more effective treatment options for advanced, unresectable, or metastatic gastric cancer. Ras-related C3 botulinum toxin substrate 1 (Rac1), a small GTP-binding protein within the Rac subfamily of the Rho GTPase family, is a critical molecule that promotes cancer cell invasion and metastasis by regulating signal transmission and promoting cell polarity. It has emerged as a key driver of tumor development and metastasis in several malignancies, including breast, lung, prostate, ovarian, gastric, and pancreatic cancers. This review summarizes the structure, regulatory dynamics, and signaling mechanisms of Rac1 in gastric cancer growth, epithelial-to-mesenchymal transition (EMT), and metastasis, as well as the roles of factors such as hypoxia, oxidative stress, and H. pylori infection. Additionally, it highlights small-molecule inhibitors targeting Rac1, miRNAs capable of suppressing Rac1, and ongoing research on Rac1-related immunotherapy. The potential of Rac1 as a therapeutic biomarker in gastric cancer and the remaining challenges in this area are also discussed. This review advances the understanding of Rac1\u2019s role in gastric cancer, provides a theoretical foundation for further studies, and supports the development of precision medicine for this disease.<\/jats:p>","DOI":"10.1186\/s12967-025-07256-x","type":"journal-article","created":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T10:35:42Z","timestamp":1762252542000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Rac1 in gastric cancer: a molecular driver of invasion, EMT, and therapeutic resistance"],"prefix":"10.1186","volume":"23","author":[{"given":"Jianwen","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yahong","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruifeng","family":"Duan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yueli","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5426-9916","authenticated-orcid":false,"given":"Ying","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,11,4]]},"reference":[{"key":"7256_CR1","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1016\/S0140-6736(20)31288-5","volume":"396","author":"EC Smyth","year":"2020","unstructured":"Smyth EC, Nilsson M, Grabsch HI, van Grieken NC, Lordick F. 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