Redox-Regulated Iron Metabolism and Ferroptosis in Ovarian Cancer: Molecular Insights and Therapeutic Opportunities

Abstract

Ovarian cancer (OC), known for its lethality and resistance to chemotherapy, is closely associated with iron metabolism and ferroptosis—an iron-dependent cell death process, distinct from both autophagy and apoptosis. Emerging evidence suggests that dysregulation of iron metabolism could play a crucial role in OC by inducing an imbalance in the redox system, which leads to ferroptosis, offering a novel therapeutic approach. This review examines how disruptions in iron metabolism, which affect redox balance, impact OC progression, focusing on its essential cellular functions and potential as a therapeutic target. It highlights the molecular interplay, including the role of non-coding RNAs (ncRNAs), between iron metabolism and ferroptosis, and explores their interactions with key immune cells such as macrophages and T cells, as well as inflammation within the tumor microenvironment. The review also discusses how glycolysis-related iron metabolism influences ferroptosis via reactive oxygen species. Targeting these pathways, especially through agents that modulate iron metabolism and ferroptosis, presents promising therapeutic prospects. The review emphasizes the need for deeper insights into iron metabolism and ferroptosis within the redox-regulated system to enhance OC therapy and advocates for continued research into these mechanisms as potential strategies to combat OC.

Keywords

• redox
• iron metabolism
• ferroptosis
• ovarian cancer
• tumor immune microenvironment
• glycolysis