Figure 1. Model of the Contribution of Iron to Ovarian Cancer Development.
Iron is elevated in the peritoneal cavity of women with endometriosis, in endometriotic cysts, and in fallopian tube fimbriae. Iron engages in Fenton reactions resulting in ROS such as hydroxyl radicals. An excess of ROS can promote cell death such as ferroptosis. However, sublethal levels of ROS may lead to increased proliferative capacity (if balanced with an increase in anti-oxidant response) thereby promoting tumorigenesis. ROS can lead to increased c-Myc transcripts, directly reduce PTEN activity, and cause DNA mutations leading to inactivation of p53 and activation of K-Ras. Tumor cells are characterized by increased iron dependence. Therefore, therapeutic strategies targeting components of the iron pathway may prove useful in treating ovarian cancer patients.