Since cisplatin and methotrexate are reported to cause cognitive impairments, and despite the different mechanisms of action engaged for cancer eradication by cisplatin (DNA-adduct formation) and methotrexate (antifolate antimetabolism), our data suggest that pathological activation of COX-2 signaling may be a common pathway of chemotherapy-induced neurotoxicity. Here, PTGS2 is linked to Cognitive impairment.