One of the mechanisms by which prostate cancer achieves castrate resistance is through de novo intratumoral production of androgens. Reactivation of androgen receptors results in promotion of cell survival and proliferation pathways despite castrate serum testosterone levels. As androgen synthesis results from conversion of the precursor cholesterol, the authors hypothesised that using the common drug simvastatin could potentially reduce proliferation and disease progression by reducing the availability of cholesterol. Using LNCaP xenograft-bearing mice, simvastatin was administered orally compared with a control group. Using subcutaneously established tumours and prostate specific antigen (PSA) as a reflection of androgen receptor activity, the results demonstrated a reduction in tumour volume and prolonged time of progression to castrate resistance in mice fed with simvastatin. Tissue extracts at eight weeks post-castration showed that simvastatin treatment suppressed intratumoral testosterone and DHT levels. These findings reflect the potential of using statins as an adjunct in the fast-developing landscape of castrate resistant prostate cancer treatment.
The potential of statin use in castrate resistant prostate cancer treatment
Reviewed by Pravisha Ravindra
Oral simvastatin administration delays castration-resistant progression and reduces intratumoral steroidogenesis of LNCaP prostate cancer xenografts.
