Ferroptosis Inducers for Prostate Cancer Therapy

Abstract

Lipid peroxidation-driven iron-dependent ferroptosis is a regulated cell death mechanism implicated in numerous diseases, such as neurological diseases, kidney injury, ischemia, and tumors, including prostate cancer. The cellular mechanisms of ferroptosis are strongly associated with iron, reactive oxygen species and amino acid metabolic pathways. Several compounds, namely ferroptosis inducers, impact these pathways and trigger ferroptosis by i) inhibiting Xc - transporter system, ii) impairing GPX4 functions and iii) oxidizing iron and polyunsaturated phospholipids. Preclinical studies show that in combination with conventional anticancer drugs, ferroptosis inducers are effective in prostate cancer and in combating the progression towards the castration-resistant disease. This review overviews the mechanisms implicated in ferroptosis and discusses the findings achieved in prostate cancer.

Keywords: GPX4; Prostate cancer; ROS; cancer therapy; ferroptosis; lipid peroxidation.