Abstract
The management of human malignancies presents ongoing challenges in modern medicine, particularly given the high morbidity and mortality associated with gastrointestinal cancers. Despite advances in therapeutic strategies, tumor complexity and evolving resistance mechanisms persistently hinder effective clinical intervention. The Regenerating gene (Reg) family comprises small secreted proteins that have garnered considerable research interest in oncology owing to their multifunctional properties. These proteins play dual roles in maintaining gastrointestinal homeostasis while simultaneously driving key pathophysiological processes including tumor proliferation, invasion, metastasis, and therapeutic resistance, thereby emerging as promising targets for early diagnosis and precision therapies. This review systematically elucidates the expression dynamics and functional roles of Reg genes in gastrointestinal malignancies, analyzing their intricate crosstalk with cellular signaling pathways and focusing particularly on tumor microenvironment modulation mechanisms. The review aims to explore the role of the Reg gene family in gastrointestinal tumors and assess its potential as both diagnostic markers and therapeutic targets in clinical practice.