Targeting ferroptosis and immune surveillance in gastric cancer with traditional Chinese medicine monomers: a dual-targeted strategy for epithelial-mesenchymal transition and angiogenesis.

Abstract

Gastric cancer (GC) is a highly prevalent and lethal malignancy worldwide. Tumor progression is driven by epithelial-mesenchymal transition (EMT) and aberrant angiogenesis, which collectively facilitate invasion, metastasis, and immune evasion. Ferroptosis, a form of programmed cell death induced by iron-dependent lipid peroxidation, has recently emerged as a promising mechanism to eliminate GC cells, overcome apoptosis resistance, and inhibit migration. Remodeling the tumor immune microenvironment to enhance immune surveillance represents another advanced therapeutic strategy. Natural compounds derived from traditional Chinese medicine (TCM), such as quercetin and curcumin, exert multi-targeted anti-tumor effects by modulating ferroptosis, EMT, angiogenesis, and the immune microenvironment. This review synthesizes evidence from both in vitro and in vivo studies supporting the role of TCM monomers in co-regulating ferroptosis and immune surveillance in GC. Furthermore, it proposes a dual-target approach against EMT and angiogenesis to advance the theoretical framework and promote the clinical application of TCM in precision oncology, thereby guiding the development of novel, low-toxicity, and high-efficacy anti-cancer agents.