Metabolic heterogeneity and functional diversity of cancer-associated fibroblasts in gastric cancer (Review)

Abstract

Gastric cancer (GC) remains a major global health challenge characterized by poor prognosis and high mortality rates, despite advances in anticancer therapies. Increasing evidence indicates that GC is a highly stromal-rich tumor, with cancer-associated fibroblasts (CAFs) serving as key stromal components of the tumor microenvironment (TME). CAFs exhibit substantial metabolic heterogeneity, such that distinct CAF subtypes demonstrate intrinsic differences and dynamic remodeling in glucose, lipid and amino acid metabolism. This metabolic reprogramming represents not only functional diversity but also an adaptive response to microenvironmental stressors, including tumor-derived signals, hypoxia, nutrient fluctuations and oxidative stress. Through these adaptations, CAFs engage in extensive crosstalk with tumor and immune cells, thereby contributing to microenvironmental remodeling. Due to their critical role and abundance in GC, CAFs have emerged as promising therapeutic targets. The present review summarizes the origins, characteristics and heterogeneity of CAFs in GC and discusses their interactions with the TME. In addition, it summarizes the metabolic heterogeneity of CAFs, explores potential metabolism-targeted therapeutic strategies and outlines the broader impact of CAFs on the TME.