PIK3CA and Familial prostate cancer: In fact, Schwartz and coworkers showed that, in PTEN-mutated prostate cancers, PI3Kalpha activity is suppressed and PI3K signaling is mediated by PI3Kbeta; a selective PI3Kbeta inhibitor only transiently inhibits AKT/mTOR signaling in these cells because it lives feedback inhibition of IGF1R and, through this mechanism, causes PI3Kalpha activation and a rebound in downstream signaling [254].