Ferroptosis as a barrier against blood cancer

Evasion from cell death is key for tumorigenesis and a major cause of treatment failure in cancer patients. Regulated cell death can be actively elicited by different genetic programs, such as those controlling apoptotic or necroptotic cell death, or by undermining critical cell survival mechanisms, especially those preventing ferroptosis. Ferroptosis is a lytic type of cell death that requires iron, characterized by plasma membrane damage that is prevented by the activity of detoxifying proteins, such as glutathione peroxidase 4 (GPX4) or ferroptosis suppressor 1 (FSP1). In cancer, resistance to apoptosis-inducing therapy has been reported to create a strong dependence on these detoxifying enzymes for tumor cell survival. Yet, it remains unclear if ferroptosis can also prevent the formation of malignant disease. Here, we plan to test if weakening ferroptosis defense systems limits the ability of cancer promoting genes (oncogenes) to generate malignant blood cells or if anti-ferroptotic defense is solely needed to keep tumor cells alive, once the disease has manifested. Answering these questions will help guide measures that will help prevent tumors to form or slow down their progression.