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, PIK3CB is linked to cancer.