Iron Metabolism Rewiring and Ferroptosis to Trigger Drug Resistance in Ovarian Cancer

Dear Colleagues,

Ovarian cancer (OC) is the second most common and lethal malignancy among female reproductive systems. Currently, the chemotherapeutic approach for OC relies on platinum-containing agents that kill cancer cells by triggering apoptosis. However, OC cells can be apoptosis-defective, thus leading to chemoresistance. Developing novel therapeutic approaches is the major goal of OC research.

Cancer cells show the so-called “iron-addicted” phenotype, characterized by a marked iron uptake and a weak iron efflux, which may represent a metabolic determinant of ferroptosis sensitivity. Ferroptosis is a type of programmed cell death driven by the iron-dependent accumulation of reactive oxygen species (ROS) to detrimental levels. Many signaling pathways are involved in this process, including the increase in intracellular iron, which increases the levels of ROS and leads to severe membrane lipid peroxidation; the repression of the cystine-glutamate antiporter (system Xc-); the inactivation of the antioxidant glutathione-dependent peroxidase 4 (GPX4); the degradation of ferritin meditated by NCOA4 via ferritinophagy. Ferroptosis induction has shown promising antitumor effects in OC cells, but the existence of undefined genetic and metabolic determinants of susceptibility has so far limited the application of ferroptosis inducers in vivo. In summary, our aim is to provide readers with novel insights into ferroptosis in OC. This Special Issue will cover the following topics: 

• Ferroptosis as an alternative strategy to target apoptosis-resistant OC cells;
• Characterization of genetic and metabolic determinants of susceptibility in ferroptosis-resistant OC cells;
• Identification of new hallmarks of ferroptosis in OC;
• Application of novel iron-based compounds as an alternative therapeutic approach to induce ferroptosis in OC.

Dr. Anna Martina Battaglia
Guest Editor

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• ferroptosis
• iron metabolism
• reactive oxygen species
• resistance mechanisms
• ovarian cancer
• ferroptosis inducer