Taken together, these findings indicate that PI3K-AKT-mTOR and RAS/MAPK signaling synergize to promote prostate cancer growth and metastatic progression, and given the frequency of co-activation of these cascades in the clinic, this provides a clear justification for exploring the combination of PI3K-AKT-mTOR and RAS/MAPK pathway inhibitors in patients with advanced prostate cancer. This evidence concerns the gene PIK3CB and Familial prostate cancer.