PIK3CA and cancer: Epidemiological evidence suggests that NSAIDs, including sulindac, which are associated with a reduced cancer risk, may be beneficial in patients whose tumors express PIK3CA genomic variants, as PIK3CA mutations lead to constitutive activation of the PI3K/AKT/mTOR pathway, upregulation of COX-2 activity, and increased PGE2 production (Cai et al., 2020).