Ferroptosis is a newly discovered form of regulated cell death. The main feature of ferroptosis is excessive membrane lipid peroxidation caused by iron-mediated chemical and enzymatic reactions. In normal cells, harmful lipid peroxides are neutralized by glutathione peroxidase 4 (GPX4). When GPX4 is inhibited, ferroptosis occurs. In mammalian cells, ferroptosis serves as a tumor suppression mechanism. Not surprisingly, in recent years, ferroptosis induction has gained attention as a potential anticancer strategy, alone or in combination with other conventional therapies. However, sensitivity to ferroptosis inducers depends on the metabolic state of the cell. Endometrial cancer (EC) is the sixth most common cancer in the world, with more than 66,000 new cases diagnosed every year. Out of all gynecological cancers, carcinogenesis of EC is mostly dependent on metabolic abnormalities. Changes in the uptake and catabolism of iron, lipids, glucose, and glutamine affect the redox capacity of EC cells and, consequently, their sensitivity to ferroptosis-inducing agents. In addition to this, in EC cells, ferroptosis-related genes are usually mutated and overexpressed, which makes ferroptosis a promising target for EC prediction, diagnosis, and therapy. However, for a successful application of ferroptosis, the connection between metabolic rewiring and ferroptosis in EC needs to be deciphered, which is the focus of this review.
Keywords: endometrial cancer; ferroptosis; metabolism; resistance.