Ferroptosis in colorectal cancer: Molecular mechanisms and regulatory crosstalk with therapeutic prospects (Review)

Colorectal cancer (CRC) is a common malignancy of the colonic and rectal epithelia.Numerous patients with CRC derive only limited and unsustained benefit from conventional chemotherapy or immunotherapy, underscoring the need for novel treatments.Ferroptosis is an iron-dependent, lipid peroxidation-driven form of regulated cell death, controlled by iron and lipid metabolism, as well as antioxidant defense pathways, which represent attractive therapeutic targets.Ferroptosis-related genes are closely linked to immune status, and metabolic reprogramming within the tumor microenvironment can modulate immune cell activation and antitumor immunity.Induction of ferroptosis suppresses CRC proliferation and overcomes resistance to cytotoxic drugs, whereas inhibition of ferroptosis may alleviate inflammatory bowel disease and limit CRC initiation in specific settings.This review summarizes the molecular basis and immunological relevance of ferroptosis in CRC, and discusses recent advances in combination strategies involving chemotherapy, immunotherapy, gut microbiota-based therapy and nanotherapy, as well as current clinical progress, potential biomarkers and translational challenges.Contents 1. Introduction 2. Molecular mechanisms of ferroptosis 3. Ferroptosis in tumor development and regulation 4. Role of ferroptosis in the TME 5. Ferroptosis inducers in CRC combination therapy 6.Effects of ferroptosis inhibition on IBD-to-CRC transition 7. Clinical research progress targeting ferroptosis 8.