Abstract
Cancer stem cells (CSCs) are a distinct subpopulation of cells within tumors, characterized by their ability to self‑renew, differentiate and promote tumorigenesis. CSCs have critical roles in the initiation, progression and therapeutic resistance of digestive tract tumors, including in esophageal, gastric, colorectal and pancreatic cancer. The present review comprehensively explores the biology of CSCs, their interactions with the tumor microenvironment and their clinical relevance in predicting patient prognosis and guiding treatment strategies. The emerging therapeutic approaches that target CSCs, including pathway inhibitors, monoclonal antibodies and combination therapies, are also discussed, highlighting the potential of these strategies to improve patient outcomes in digestive tract cancer types. Additionally, future research directions and challenges in developing effective CSC‑targeted therapies are addressed, emphasizing the need for innovative strategies to overcome treatment resistance and increase therapeutic efficacy.