Ferroptosis in gastrointestinal cancer: from mechanisms to implications. (1st May 2023) - Zhang, Ruoxi
Abstract: Ferroptosis is a form of regulated cell death that is initiated by excessive lipid peroxidation that results in plasma membrane damage and the release of damage-associated molecular patterns. In recent years, ferroptosis has gained significant attention in cancer research due to its unique mechanism compared to other forms of regulated cell death, especially caspase-dependent apoptotic cell death. Gastrointestinal (GI) cancer encompasses malignancies that arise in the digestive tract, including the stomach, intestines, pancreas, colon, liver, rectum, anus, and biliary system. These cancers are a global health concern, with high incidence and mortality rates. Despite advances in medical treatments, drug resistance caused by defects in apoptotic pathways remains a persistent challenge in the management of GI cancer. Hence, exploring the role of ferroptosis in GI cancers may lead to more efficacious treatment strategies. In this review, we provide a comprehensive overview of the core mechanism of ferroptosis and discuss its function, regulation, and implications in the context of GI cancers. Highlights: Ferroptosis is an iron-dependent cell death driven by excessive lipid peroxide accumulation on membranes. The major defense system of ferroptosis is the SLC7A11-GSH-GPX4 axis. Calcium-dependent ESCRT-III can repair membrane damage during ferroptosis. Ferroptosis has both pro-tumor and anti-tumor effects in GI cancers.