An inducible form of the terminal PGE2 synthase, mPGES-1, is elevated in colorectal cancer (CRC), often in association with COX-2. mPGES-1 has been suggested as an alternative target to COX-2 for CRC prevention, with potentially lower cardiovascular toxicity. The efficacy of targeting mPGES-1 was examined in mouse genetic and carcinogen-induced models. Genetic deletion of mPGES-1 significantly suppressed the growth of Apc-initiated intestinal tumors, and the formation of carcinogen-induced preneoplastic aberrant crypt foci (ACF) in the colon. Interestingly, nuclear translocation of Β-catenin in ACF was blocked in mPGES-1 null mice, indicating that the Wnt pathway mediates the tumor-promoting action of mPGES-1 and PGE². These data support the feasibility of targeting mPGES-1 for CRC prevention, which may be a safer approach relative to traditional NSAIDs and selective COX-2 inhibitors. For details, see the article by Nakanishi and colleagues on page 3251 of this issue.