Statins and prostate cancer—hype or hope? The biological perspective

• Published in: Prostate cancer and prostatic diseases Vol. 25; no. 4; pp. 650 - 656
• Main Authors: Longo, Joseph, Freedland, Stephen J., Penn, Linda Z., Hamilton, Robert J.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-04-2022; Nature Publishing Group
• Subjects: 631/67/1059; 631/67/2327; 631/67/589/466; Anticancer properties; Antineoplastic Agents - therapeutic use; Antitumor agents; Apoptosis; Biomedical and Life Sciences; Biomedicine; Cancer Research; Cholesterol; Coenzyme A; Deregulation; Humans; Hydroxymethylglutaryl-CoA reductase; Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology; Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use; Male; Metabolic pathways; Metabolism; Metabolites; Mevalonate pathway; Mevalonic Acid - metabolism; Mevalonic Acid - pharmacology; Mevalonic Acid - therapeutic use; Prostate cancer; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - metabolism; Reductases; Reproductive Medicine; Review Article; Risk management; Statins
• ISSN: 1365-7852; 1476-5608
• DOI: 10.1038/s41391-022-00557-y

Growing evidence suggests that men prescribed a statin for cholesterol control have a lower risk of advanced prostate cancer (PCa) and improved treatment outcomes; however, the mechanism by which statins elicit their anti-neoplastic effects is not well understood and is likely multifaceted. Statins are potent and specific inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), the rate-limiting enzyme of the mevalonate (MVA) metabolic pathway. This two-part series is a review of the observational and experimental data on statins as anti-cancer agents in PCa. In this article, we describe the functional role that deregulated MVA metabolism plays in PCa progression and summarize the biological evidence and rationale for targeting the MVA pathway, with statins and other agents, for the treatment of PCa.