Perspectives on mTOR inhibitors for castration-refractory prostate cancer.

The phosphatidylinositol 3'-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling pathway contributes to prostate cancer progression and transition to androgen-independent disease. Furthermore, recent microarray analysis demonstrates that this pathway is often deregulated during prostate cancer progression. Thus, targeting of PI3K/AKT/mTOR may present a promising therapy for castration-refractory prostate cancer (CRPC). In recent years, several interesting strategies have been developed that interfere with distinct components of the PI3K/AKT/mTOR cascade. This article discusses many of the mechanisms involved, specifically in the context of prostate cancer. In addition, we present an overview of preliminary data on the activity of mTOR inhibitors and on the key steps to evaluate which of these compounds are most suitable for the treatment of prostate cancer. Particular emphasis is also placed on the development of novel perspectives to improve the poor prognosis of patients with CRPC.