| Tumor-associated macrophages (TAMs) and ferroptosis are recognized as pivotal regulators in shaping the immunosuppressive tumor microenvironment (TME) and driving the malignant progression of digestive system malignancies. Elucidating their underlying molecular mechanisms and evaluating their translational potential have become prominent areas of contemporary oncological research. In this review, we systematically delineate the bidirectional crosstalk between TAMs and ferroptosis in digestive system cancers, including gastric cancer, hepatocellular carcinoma (HCC), and colorectal cancer (CRC). In addition, we extend the discussion to inflammation-associated premalignant conditions, such as Helicobacter pylori–associated gastritis, ulcerative colitis (UC), and hepatic fibrosis, highlighting their roles in tumor initiation and progression. Moreover, we comprehensively summarize emerging therapeutic strategies targeting TAMs and ferroptosis, and critically evaluate recent advances in their clinical translation. We also address current challenges and limitations in this field. Collectively, this review aims to provide a theoretical framework and potential directions for the development of precision medicine approaches in digestive system malignancies. |
