Targeting intratumoral androgens: statins and beyond

Abstract

While initially effective, androgen deprivation therapy (ADT) is not curative, and nearly all men with advanced prostate cancer will eventually progress to the more resistant, and ultimately lethal form of the disease, so called castration-resistant prostate cancer (CRPC). The maintenance of androgens within the prostate cancer microenvironment likely represents one of the key mechanisms by which this transition from hormone-sensitive to CRPC occurs. This can be accomplished either through intratumoral androgen biosynthesis or the active transport of androgens and androgenic precursors into the tumor microenvironment. More recently, preclinical and clinical data supported therapeutic strategies that seek to target these two mechanisms, either through the use of drugs that impair androgen biosynthesis (e.g. inhibiting the steroidogenic enzymes CYP17 and AKR1C3 with abiraterone and indomethacin, respectively) or drugs that inhibit the SLCO transporters responsible for importing androgens (e.g. statins).

Dimensions of Niche-Induced Anti-Apoptosis of Therapeutically Resistant Neoplasms in Radio-Chemo-Therapy

“…Persistence of androgens in the prostate microenvironment is a key mechanism by which transition from hormone-sensitive to castration-resistant prostate cancer develops [12].…”

Synergistic antitumor interaction of valproic acid and simvastatin sensitizes prostate cancer to docetaxel by targeting CSCs compartment via YAP inhibition

“…Multiple epidemiological evidences suggested that statins could reduce risk, tumor aggressiveness, and mortality in PCa [ 15 ]. Moreover, a direct antitumor effect of statins in monotherapy [ 16 – 18 ] and in combination with both androgen-signaling inhibitors [ 17 , 19 ] or DTX [ 20 ] has been shown.…”