Taken together, these data suggest that the salicylate moiety of aspirin may significantly counteract the PIK3CA mutation-triggered overactivity of several relevant effectors of the PIK3 pathway, e.g., by inhibiting NF-κB-dependent signal transduction and by downregulating COX-2 expression, thus possibly contributing to the beneficial effects of aspirin on PIK3CA-mutant CRC. The gene discussed is PIK3CA; the disease is colorectal carcinoma.