The Role of Iron Chelation Therapy in Prostate Cancer

Prostate cancer remains a leading cause of cancer related morbidity and mortality in men, and novel therapeutic strategies are urgently required to overcome resistance to conventional treatments. Altered iron metabolism is increasingly recognized as a hallmark of prostate cancer, with tumor cells displaying enhanced iron uptake, decreased efflux, and dependence on iron dependent enzymes to sustain rapid growth and survival. These vulnerabilities provide a strong rationale for iron chelation therapy as a potential antitumor approach. A range of chelating agents, including clinically approved compounds such as deferiprone (DFP), deferasirox (DFX), and deferoxamine (DFO), as well as experimental thiosemicarbazones and natural polyphenols, have demonstrated inhibitory effects on prostate cancer cell proliferation, invasion, and survival in preclinical models. Molecular mechanistic investigations reveal that iron chelation disrupts redox balance, impairs mitochondrial activity, induces apoptosis and ferroptosis, and activates tumor suppressor pathways such as N-myc downstream regulated 1 (NDRG1). While early clinical investigations of iron chelators in prostate cancer have produced limited responses, ongoing research highlights opportunities to enhance efficacy through nanoparticle formulations, optimized drug delivery, and combination with established therapies. This review provides a comprehensive overview of the molecular basis, preclinical evidence, and clinical observations of iron chelation in prostate cancer, highlighting its therapeutic potential while delineating the translational barriers that need to be overcome for successful clinical application.