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

Prostate Cancer and Prostatic Diseases volume 25, pages 650–656 (2022)Cite this article

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Abstract

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.

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Fig. 1: Schematic of the MVA pathway and its regulation by SREBP2.
Fig. 2: Targeting the MVA pathway and its restorative feedback loop in PCa.
Fig. 3: Mechanisms of MVA pathway deregulation in PCa.

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Acknowledgements

LZP holds a Tier 1 Canada Research Chair in Molecular Oncology and is supported by research funding from the Canadian Institutes of Health Research (CIHR; FRN: 178393) and the Canadian Cancer Society (#706394). RJH is supported by a Canadian Urological Association Scholarship Foundation (CUASF) Career Development Award. JL is supported by a CIHR Doctoral Research Award.

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Authors and Affiliations

  1. Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada

    Joseph Longo, Linda Z. Penn & Robert J. Hamilton

  2. Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada

    Joseph Longo & Linda Z. Penn

  3. Division of Urology, Department of Surgery, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA

    Stephen J. Freedland

  4. Section of Urology, Durham VA Medical Center, Durham, NC, USA

    Stephen J. Freedland

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Conceptualization: JL, LZP, RJH; Writing, Reviewing & Editing: JL, SJF, LZP, RJH. All authors approved the final version of the paper.

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Longo, J., Freedland, S.J., Penn, L.Z. et al. Statins and prostate cancer—hype or hope? The biological perspective. Prostate Cancer Prostatic Dis 25, 650–656 (2022). https://doi.org/10.1038/s41391-022-00557-y

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