The current evidence on statin use and prostate cancer prevention: are we there yet?

Abstract

An increasing amount of data supports an inverse association between statin use and cancer risk. The findings for prostate cancer, particularly advanced disease, are the most promising of all cancers studied. Use of these agents seems to also be associated with improved prostate-cancer-specific survival, particularly in men undergoing radiotherapy, suggesting usefulness of statins in secondary and tertiary prevention. Some study results might be influenced by increased PSA screening and health-conscious behaviour in statin users but these factors are unlikely to completely account for observed beneficial effects. The epidemiological evidence is supported by preclinical studies that show that statins directly inhibit prostate cancer development and progression in cell-based and animal-based models. The antineoplastic effect of statins might arise from a number of cholesterol-mediated and non-cholesterol-mediated mechanisms that affect pathways essential for cancer formation and progression. Understanding these mechanisms is instrumental in drug discovery research for the development of future prostate cancer therapeutics, as well as in designing clinical trials to test a role for statins in prostate cancer prevention. Currently, sufficient data are lacking to support the use of statins for the primary prevention of prostate cancer and further research is clearly warranted. Secondary and tertiary prevention trials in men who have been diagnosed with prostate cancer might soon be performed.

Statin Use, Serum Lipids, and Prostate Inflammation in Men with a Negative Prostate Biopsy: Results from the REDUCE Trial

“…Together, these findings support a role for cholesterol, and cholesterol-lowering interventions, in prostate cancer [9]. Beyond cholesterol-lowering effects, statins may also have off-target effects on the prostate via non-cholesterol mediated mechanisms [1]. Clinical trials show that statins lower serum C-reactive protein [10, 11] and reduce cytokine production by circulating lymphocytes [12] independent of their cholesterol-lowering effects, demonstrating that statins lower systemic inflammation.…”

“…Statin use is associated with reduced risk of advanced prostate cancer [1]. Statins lower serum cholesterol by inhibiting 3-hydroxy-3-methyl glutaryl coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme for cholesterol synthesis.…”

The role of statins as therapeutic agents in cancer

“…Hydrophilic statin pravastatin is more hepatoselective than lipophilic statins cerivastatin, simvastatin, lovastatin, mevastatin, atorvastatin, rosuvastatin and fluvastatin, whereupon is pravastatin actively transported into the liver by members of the organic anion transporting polypeptide family (also known as OATPs). In contrast, lipophilic statins enter the liver by passive diffusion (Alfaqih et al 2017). The sodium-independent organic anion transporter protein-1B1 (OATP1B1) is exclusively expressed in liver (Menter et al 2011).…”

“…This effect was abolished by substitution of mevalonate or GGPP (Woschek et al 2016). Moreover, high sensitivity of cells to irradiation-induced cell death in G1 phase can be used in cancer radiotherapy (Chan et al 2003;Alfaqih et al 2017). These findings suggest that statins inhibit proliferation in cancer cells by various mechanisms, including reduction of prenylation and cholesterol depletion.…”

“…The epidemiological evidence is supported by preclinical studies showing that statins directly inhibit prostate cancer development and progression in cell-based and animal-based models. Currently, there are no sufficient data to support the use of statins for the primary prevention of prostate cancer and further research is needed (Alfaqih et al 2017).…”