page_title: Ferroptosis
section_title: Role of ferroptosis in cancer treatment
hierarchical_section_title: Ferroptosis / Role of ferroptosis in cancer treatment
caption_attribution_description: English: Mechanism in which ferroptosis is induced by the Xc- System and Gpx4 activity, in relation to being used as a potential treatment for cancer.
context_page_description: Ferroptosis is a type of programmed cell death dependent on iron and characterized by the accumulation of lipid peroxides, and is genetically and biochemically distinct from other forms of regulated cell death such as apoptosis. Ferroptosis is initiated by the failure of the glutathione-dependent antioxidant defenses, resulting in unchecked lipid peroxidation and eventual cell death. Lipophilic antioxidants and iron chelators can prevent ferroptotic cell death. Although the connection between iron and lipid peroxidation has been appreciated for years, it was not until 2012 that Brent Stockwell and Scott Dixon coined the term ferroptosis and described several of its key features.
  Researchers have identified roles in which ferroptosis can contribute to the medical field such as in aiding in cancer treatments where this form of cell death can be induced in the human body. Ferroptosis activation plays a regulatory role on growth of tumor cells in the human body. However, the positive effects of ferroptosis could be potentially neutralized by its disruption of metabolic pathways and disruption of homeostasis in the human body.
context_section_description: Ferroptosis is a more controlled form of programmed cell death. With small molecules inducing ferroptosis, it inhibits tumor growth and increases drug resistance. It is still unknown the exact mechanism in which ferroptosis inhibits tumor growth, but based on early experiments, it could be used to treat tumor cells and ultimately cancer.
  Based on the figure shown, initiating ferroptosis can be done by eliminating GPX4 activity through Xc- (erastin mediated). The inhibition or degradation of GPX4 by erastin or RSL3 has been noticed to be the primary mechanism that will trigger ferroptosis. Since ferroptosis is an iron dependent mechanism, an accumulation of lipid ROS kills the cells that have begun to undergo ferroptosis and eliminates them completely.
  Ferroptosis can be used to treat several different types of cancer, each seemingly different forms of the disease. This method of cell death has been tested either in mice, or is in the early stages of research and has not yet been fully tested. This includes cancer types such as:
  Breast
  Acute myeloid leukemia
  Pancreatic ductal adenocarcinoma
  Ovarian
  B cell lymphoma
  Renal cell carcinomas
  Lung
  Glioblastoma
  These forms of cancer have been hypothesized to be highly sensitive to ferroptosis, or react to erastin or Xc- in a way that minimizes the tumor cells or responds to this treatment with a result of cell death. An upregulation of iron levels has also been seen to induce ferroptosis in certain types of cancer, such as breast cancer. Breast cancer cells have exhibited vulnerability to ferroptosis via a combination of siramesine and lapatinib.  These cells also exhibited an autophagic cycle independent of ferroptotic activity, indicating that the two different forms of cell death could be controlled to activate at specific times following treatment.
caption: Initiation of Ferroptosis By Inhibition of Xc- System of Gpx4 Activity
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