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Life sciences · Journal article
Annals of Gastroenterological Surgery · October 27, 2026
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ABSTRACT Metastasis has traditionally been investigated and treated as a single manifestation of gastric cancer progression. Although this approach has generated important biological insights and effective systemic therapies, it may obscure route‐dependent vulnerabilities. Lymphatic, peritoneal, and hematogenous metastases require cancer cells to traverse different anatomical routes, overcome distinct barriers, and adapt to different microenvironments. This review therefore distinguishes broadly metastasis‐associated mechanisms from pattern‐associated candidates and reserves pattern‐specific designation for evidence based on direct route comparison, pattern prediction, or route‐selective functional experiments. We examine representative molecular determinants and link their identification in surgical specimens to functional validation, biomarker development, and drug discovery. Evidence is most mature for peritoneal dissemination, whereas lymph‐node‐specific determinants remain less developed. The SYT13/ASO‐4733 program is presented as an illustrative translational case: Intraperitoneal ASO‐4733 has entered first‐in‐human Phase I evaluation, but clinical efficacy has not been established. For any candidate, clinical utility requires independent validation, incremental value beyond established clinicopathological factors, and a defined effect on decision‐making. Rigorously collected, rapidly processed, and clinically annotated surgical biospecimens remain indispensable. Reframing gastric cancer metastasis by route may expand opportunities for precise risk prediction, rational delivery, and biologically coherent early‐phase trials.