Ferroptosis in ovarian cancer: Regulation, immunity, and therapeutic potential with the tumor microenvironment

Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, represents a pivotal and translationally promising target in ovarian cancer management. This review systematically explores the dual role of ferroptosis in inhibiting tumor growth while simultaneously promoting immune evasion and cancer recurrence. We synthesize current evidence on the dynamic interplay between ferroptosis, tumor progression, and the immunosuppressive tumor microenvironment in ovarian cancer. We highlight key biological features of ovarian cancer, including its iron-rich ascites and lipid-abundant omentum, create a unique context for ferroptosis modulation. Crucially, ferroptosis not only influences cancer cell survival and chemoresistance but also profoundly shapes antitumor immunity by affecting T cell function, macrophage polarization, and dendritic cell activity. We discuss how targeting ferroptosis through inducers, nanoparticle delivery systems, or combination with PARPi and immunotherapy can overcome cisplatin and PARPi resistance and reverse immunosuppression. Despite clinical challenges such as heterogeneity and recurrent disease, ferroptosis-related gene signatures and emerging noninvasive detection methods offer avenues for patient stratification. We conclude that integrating ferroptosis-targeted strategies into the therapeutic arsenal holds significant potential to improve outcomes for ovarian cancer patients.