Ferroptosis in colorectal cancer: Potential mechanisms and effective therapeutic targets

Colorectal cancer (CRC) is a common malignant tumor characterized by unchecked division and survival of abnormal cells in the colon or rectum with high morbidity and mortality. Despite the rapid development of early screening methods and improved therapies, the prognosis of CRC is not satisfactory. Identification of new biomarkers for early detection and development of more effective therapies are still urgent tasks in current studies to achieve ideal treatment of CRC. Ferroptosis is a recently emerged novel regulated form of cell death characterized by a massive accumulation of iron-dependent lipid peroxidates, making it morphologically and molecularly distinct from apoptosis, cell death, and autophagy. Accumulating studies have shown that induction of ferroptosis in CRC successfully eliminates cancer cells resistant to other modes of cell death. Thus, ferroptosis may become a new direction for the design of CRC therapy. Although many research articles have investigated the possible roles of ferroptosis in CRC, a study that summarizes the main findings, including the regulators and mechanisms of action, of ferroptosis in CRC is not available. Herein, the studies in recent literature regarding the roles of ferroptosis on the progression and treatment of CRC were summarized, mainly focusing on molecular and biological mechanisms in vitro and in vivo. In particular, the roles of numerous ferroptosis regulators, such as SLC7A11, reactive oxygen species (ROS), glutathione (GSH), and iron, in CRC, were discussed and the application of ferroptosis-associated genes for the early diagnosis and prognosis of CRC was explored. In addition, an outlook for future studies of ferroptosis in CRC treatment and the possible barriers and the corresponding solutions were discussed.