Our results suggest AKT inhibitors may also be superior to pan-PI3K inhibition in breast and prostate cancers harboring loss of PTEN, however in the context of PIK3CA mutant PTEN wild-type cancers there is limited efficacy to AKT inhibition and targeting p110α is superior, secondary to dual suppression of downstream PI3K and MAPK signaling. Here, PIK3CA is linked to Familial prostate cancer.