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Although reactive oxygen species (ROS) have long been implicated in tumor biology, current models incompletely explain how chronic nicotine selectively reprograms gastric epithelial signaling. This review advances the concept of redox rewiring, whereby nicotine establishes a persistent oxidative state that orchestrates multiple oncogenic programs\n                      <jats:italic toggle=\"yes\">via<\/jats:italic>\n                      spatially compartmentalized NOX signaling.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Recent Advances:<\/jats:title>\n                    <jats:p>\n                      We synthesize evidence for a unified model wherein nicotine activates nAChR\/\u03b2-AR signaling, Ca\n                      <jats:sup>2+<\/jats:sup>\n                      influx, PKC, and compartmentalized NOX-derived ROS to generate distinct oncogenic outputs. Beyond the established NOX\/ROS\/NF-\u03baB\/MAPK-driven IL-8 and MMP-9 axes, we integrate emerging evidence into three interconnected modules governing EMT\/metastasis (ABL1\/STAT3\/COX-2\/periostin), survival\/chemoresistance (ERK\/GLI1\/Bcl-2), and invasion\/immune evasion (miR-21\/PDCD4). Collectively, these circuits suggest that ROS function not merely as damaging byproducts but as spatially organized signaling mediators dictating tumor behavior.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Critical Issues:<\/jats:title>\n                    <jats:p>\n                      A major challenge is distinguishing established mechanisms from incompletely validated models. The three proposed axes are testable hypotheses requiring experimental validation. Most data derive from\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      studies with nonphysiologic nicotine concentrations, and artifacts from nonspecific ROS probes are common. Compensatory pathway activation and multi-target effects of natural products remain underexplored.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Future Directions:<\/jats:title>\n                    <jats:p>\n                      We outline a precision-redox oncology roadmap linking pathway-specific biomarkers, mechanistically matched natural products, and biomarker-enriched trials. Priorities include genetic validation of the three axes, time-resolved ROS imaging, and pulsed natural product regimens. By reframing nicotine-driven GC as adaptive redox network remodeling, this review provides a framework for prevention, stratification, and next-generation therapy.\n                      <jats:italic toggle=\"yes\">Antioxid. Redox Signal.<\/jats:italic>\n                      00, 000\u2013000.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/15230864261483986","type":"journal-article","created":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T02:02:37Z","timestamp":1788314557000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Redox Rewiring in Nicotine-Driven Gastric Carcinogenesis: Uncovering ROS-Dependent Oncogenic Circuits"],"prefix":"10.1177","author":[{"given":"Xilei","family":"Liu","sequence":"first","affiliation":[{"name":"School of Public Health, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, People\u2019s Republic of China."},{"name":"Jiangxi Provincial Key Laboratory of Disease Prevention and Public Health, Nanchang University, Nanchang, Jiangxi, People\u2019s Republic of China."},{"name":"Chongqing Research Institute of Nanchang University, Tongnan, Chongqing, People\u2019s Republic of China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinhan","family":"Jiang","sequence":"additional","affiliation":[{"name":"School of Public Health, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, People\u2019s Republic of China."},{"name":"Jiangxi Provincial Key Laboratory of Disease Prevention and Public Health, Nanchang University, Nanchang, Jiangxi, People\u2019s Republic of China."},{"name":"Chongqing Research Institute of Nanchang University, Tongnan, Chongqing, People\u2019s Republic of China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boxuan","family":"Xie","sequence":"additional","affiliation":[{"name":"School of Public Health, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, People\u2019s Republic of China."},{"name":"Jiangxi Provincial Key Laboratory of Disease Prevention and Public Health, Nanchang University, Nanchang, Jiangxi, People\u2019s Republic of China."},{"name":"Chongqing Research Institute of Nanchang University, Tongnan, Chongqing, People\u2019s Republic of China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongwei","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Public Health, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, People\u2019s Republic of China."},{"name":"Jiangxi Provincial Key Laboratory of Disease Prevention and Public Health, Nanchang University, Nanchang, Jiangxi, People\u2019s Republic of China."},{"name":"Chongqing Research Institute of Nanchang University, Tongnan, Chongqing, People\u2019s Republic of China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianming","family":"Zhou","sequence":"additional","affiliation":[{"name":"School of Public Health, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, People\u2019s Republic of China."},{"name":"Jiangxi Provincial Key Laboratory of Disease Prevention and Public Health, Nanchang University, Nanchang, Jiangxi, People\u2019s Republic of China."},{"name":"Chongqing Research Institute of Nanchang University, Tongnan, Chongqing, People\u2019s Republic of China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tong","family":"Zhou","sequence":"additional","affiliation":[{"name":"School of Public Health, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, People\u2019s Republic of China."},{"name":"Jiangxi Provincial Key Laboratory of Disease Prevention and Public Health, Nanchang University, Nanchang, Jiangxi, People\u2019s Republic of China."},{"name":"Chongqing Research Institute of Nanchang University, Tongnan, Chongqing, People\u2019s Republic of China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-7918-3138","authenticated-orcid":false,"given":"Huai","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Public Health, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, People\u2019s Republic of China."},{"name":"Jiangxi Provincial Key Laboratory of Disease Prevention and Public Health, Nanchang University, Nanchang, Jiangxi, People\u2019s Republic of China."},{"name":"Chongqing Research Institute of Nanchang University, Tongnan, Chongqing, People\u2019s Republic of China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,9,1]]},"reference":[{"issue":"3","key":"e_1_3_4_2_1","first-page":"219","article-title":"Reactive oxygen species signaling in cancer: Comparison with aging","volume":"2","author":"Afanas\u2019ev I","year":"2011","unstructured":"Afanas\u2019ev I. 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