PIK3CA and colorectal carcinoma: As aspirin irreversibly inhibits the activity of COX-2, a rate limiting enzyme in the synthesis of prostaglandin E2 (PGE2), and activation of PI3K-AKT pathway upregulates COX2 expression, it was hypothesized that constitutional activation of this signaling pathway by PIK3CA mutations might be predictive of aspirin’s benefits for CRC patients.