Three May Be Better Than Two: A Proposal for Metformin Addition to PI3K/Akt Inhibitor-antiandrogen Combination in Castration-resistant Prostate Cancer

Prostate cancer is a prevalent malignant disease. Castration-resistant prostate cancer (CRPC) is a poor prognosis form that develops upon resistance to first-line androgen deprivation therapy. Intensive research is ongoing to find efficient therapeutics for this refractory state. Actually, the combination of PI3K/Akt inhibitors with new-generation antiandrogens is among the most promising therapeutic schemes, although not yet at the optimal level. Metformin effects on prostate cancer, notably its therapeutic targets shared with antiandrogens and/or PI3K/Akt inhibitors, are reviewed in this article. From that, the hypothesis of PI3K/Akt-antiandrogens dual blockade optimization by metformin addition in CRPC will be deduced.