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Ferroptosis Inducers for Prostate Cancer Therapy

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CURRENT MEDICINAL CHEMISTRY
卷 29, 期 24, 页码 4185-4201

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BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/0929867329666220111120924

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Prostate cancer; ferroptosis; lipid peroxidation; GPX4; ROS; cancer therapy

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Lipid peroxidation-driven iron-dependent ferroptosis is a regulated cell death mechanism implicated in various diseases, such as neurological diseases, kidney injury, ischemia, and tumors, including prostate cancer. Ferroptosis inducers targeting iron, reactive oxygen species, and amino acid metabolic pathways show promise in effectively treating prostate cancer and combating the progression towards castration-resistant disease.
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 X-c(-) 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.

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