Current insights into gastric cancer stem cells: Mechanisms and therapeutic prospects

Gastric cancer remains a leading cause of cancer-related mortality worldwide, driven significantly by gastric cancer stem cells (GCSCs), a unique subset of cells characterized by self-renewal, multipotency, and therapy resistance. This review synthesizes recent advancements in understanding GCSCs, focusing on their definition, characteristics, identification, isolation and role in tumor growth, metastasis, and resistance to conventional treatments. Key surface markers such as CD44, CD133, leucine rich repeat containing G protein-coupled receptor 5 (LGR5), and aquaporin 5 (AQP5) are critical for GCSC identification, with their expression linked to poor prognosis and tumor progression. The review summarizes mechanisms like epithelial-mesenchymal transition (EMT) and Wnt/β-catenin signaling that enhance GCSC stemness and malignancy. It also highlights emerging targeted therapies, including antibody-based approaches including CD44v6-specific antibodies, inhibitors like sulfasalazine, and novel immunological strategies such as chimeric antigen receptor T (CAR-T) cell therapy, aimed at eradicating GCSCs. By elucidating the molecular and functional roles of GCSCs, this review underscores GCSCs as therapeutic targets and provides a foundation for developing precision medicine strategies to improve gastric cancer outcomes.