From epithelial-mesenchymal transition to liquid biopsy: mechanisms of gastric cancer metastatic dissemination and circulating biomarker-guided anti-recurrence strategies

Recurrence remains a major cause of death after curative-intent treatment of gastric cancer, and imaging may miss residual disease before macroscopic relapse. This narrative review links the biology of dissemination with circulating biomarkers and potential strategies for recurrence prevention within a gastric cancer-specific conceptual framework. We examine epithelial-mesenchymal transition and plasticity, circulating tumor cells, and pre-metastatic niche formation, with particular attention to diffuse-type tumors and peritoneal dissemination. We then assess circulating tumor DNA (ctDNA) and molecular residual disease (MRD) as indicators of tumor-derived DNA shedding and recurrence risk. These domains are biologically related but do not form an obligatory linear sequence: plasma ctDNA is not a direct measure of epithelial-mesenchymal transition or niche activity. Postoperative ctDNA positivity is associated with increased recurrence risk, whereas negative results require caution in low-shedding and isolated peritoneal disease. We distinguish established perioperative treatment benefits from MRD-guided escalation or de-escalation, for which no survival benefit has yet been shown in gastric cancer. HER2- and claudin-18.2-directed treatments are discussed in their tested disease settings and require appropriate target assessment independently of MRD status. Preclinical niche-directed approaches, including traditional Chinese medicine studies, provide hypotheses for further investigation. The framework links mechanistic and clinical research while separating prognostic validity from evidence that biomarker-guided intervention improves patient outcomes.