Ferroptosis in cancer and Beyond-volume II

It has been 11 years since Brent Stockwell identified and named ferroptosis [1]. Ferroptosis results from the iron-dependent lipoxidation at various cellular membrane structures.Searching the PubMed database by using the keyword "ferroptosis", you can get more than 8000 papers. Why has ferroptosis received so intensive studies? There are at least three fundamental reasons. First, ferroptosis has unique mechanism distinct from other known regulated cell death types. Ferroptosis is tightly associated with cell metabolism, such as amino acid, iron, and ROS metabolism. There are three key elements for ferroptosis: substrate of lipid peroxidation, executor of lipid peroxidation, and anti-ferroptosis system [2].The balance between the three elements dictates the sensitivity of a cell to ferroptosis.Second, the multiple ways to induce ferroptosis result in a complex regulatory network of it.Many pathways are involved in ferroptosis mediation. Key factors regulating ferroptosis including GPX4, p53, FSP1, and ALOXs have been identified [2][3][4][5]. However, new pathways and regulators are still emerging. Third, ferroptosis participates in the regulation of numerous physiological or pathological processes, such as normal development, degenerative diseases, ischemic injuries, immune system activities, and particularly cancer. This fact renders ferroptosis amazing potential as a therapeutic target in many diseases [6].