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Despite improvements in screening and treatment, the progressive nature of precancerous lesions\u2014such as atrophic gastritis, intestinal metaplasia and dysplasia\u2014necessitates effective prevention strategies. This review evaluates the role of chemoprevention in GC, focusing on agents designed to target these precancerous lesions. The interventions examined include nonsteroidal anti-inflammatory drugs (NSAIDs), COX-2 inhibitors, antioxidants, vitamins, folic acid, bioactive compounds, traditional herbal medicines and emerging agents like metformin. Additionally, the potential of oxygen radical scavengers, anti-inflammatory agents and pathway-specific inhibitors is explored. While promising, the clinical effectiveness of these agents varies, and significant challenges remain in translating preclinical successes into clinical practice. Large-scale clinical trials are essential to validate these strategies and determine their role in GC prevention, particularly for high-risk populations. Integrating chemoprevention with existing GC management protocols may offer a more comprehensive approach to reducing GC incidence and improving outcomes.<\/jats:p>","DOI":"10.1093\/qjmed\/hcaf030","type":"journal-article","created":{"date-parts":[[2025,1,29]],"date-time":"2025-01-29T19:19:22Z","timestamp":1738178362000},"page":"385-409","source":"Crossref","is-referenced-by-count":10,"title":["Chemoprevention strategies for precancerous gastric lesions beyond <i>Helicobacter pylori<\/i> eradication"],"prefix":"10.1093","volume":"118","author":[{"given":"Tai","family":"Zhang","sequence":"first","affiliation":[{"name":"Peking University Traditional Chinese Medicine Clinical Medical School (Xiyuan), Peking University Health Science Center , Beijing,","place":["People\u2019s Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0391-3895","authenticated-orcid":false,"given":"Xudong","family":"Tang","sequence":"additional","affiliation":[{"name":"Peking University Traditional Chinese Medicine Clinical Medical School (Xiyuan), Peking University Health Science Center , Beijing,","place":["People\u2019s Republic of China"]},{"name":"Institute of Digestive Diseases, Xiyuan Hospital, China Academy of Chinese Medical Sciences , Beijing,","place":["People\u2019s Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,1,28]]},"reference":[{"key":"2025090918222633000_hcaf030-B1","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1136\/gutjnl-2024-333227","article-title":"Epidemiology of gastrointestinal cancers: a systematic analysis from the Global Burden of Disease Study 2021","volume":"74","author":"Danpanichkul","year":"2024","journal-title":"Gut"},{"key":"2025090918222633000_hcaf030-B2","first-page":"209","article-title":"Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J Clin"},{"key":"2025090918222633000_hcaf030-B3","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1016\/j.cgh.2019.07.045","article-title":"Burden of gastric cancer","volume":"18","author":"Thrift","year":"2020","journal-title":"Clin Gastroenterol Hepatol"},{"key":"2025090918222633000_hcaf030-B4","doi-asserted-by":"crossref","first-page":"2452","DOI":"10.3748\/wjg.v29.i16.2452","article-title":"Updates on global epidemiology, risk and prognostic factors of gastric cancer","volume":"29","author":"Yang","year":"2023","journal-title":"World J Gastroenterol"},{"key":"2025090918222633000_hcaf030-B5","doi-asserted-by":"crossref","first-page":"207","DOI":"10.21147\/j.issn.1000-9604.2022.03.04","article-title":"National guidelines for diagnosis and treatment of gastric cancer 2022 in China (English version)","volume":"34","author":"National Health Commission of the People\u2019s Republic of China","year":"2022","journal-title":"Chin J Cancer Res"},{"key":"2025090918222633000_hcaf030-B6","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1136\/gutjnl-2019-320234","article-title":"Is gastric cancer becoming a rare disease? 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