Targeting the remodeled peritoneal ecosystem: a paradigm shift from tumor cells to the microenvironment in gastric cancer peritoneal metastasis

Peritoneal metastasis (PM) is the most common form of organ-specific metastasis in advanced gastric cancer (GC), and is driven by the dynamic interplay between cancer cells and the tumor microenvironment (TME). This review elaborates on the mechanisms through which cancer cells utilize metabolic reprogramming, mechanical stress, and neural control to shape the microenvironment conducive to tumor growth. It also describes the metastatic cascade of their active dissemination and colonization processes of cancer cells within the peritoneal cavity. Finally, on the basis of these mechanistic insights, we propose a three-step strategy that dismantle physical barriers, blocks nutrient supply, and reverses immune suppression. The aim of this study to transform PM from a treatment challenge into a manageable disease, further improving disease prognosis.