Chemoprevention of colorectal cancer by inhibition of cyclooxygenase-2 derived prostaglandin E₂ signaling: Recent advances in basic biology

Experimental evidence collected over the past decade has revealed that targeting cyclooxygenase-2 (COX-2) may have some efficacy for chemoprevention of cancer. However, recent safety concerns over the long-term use of COX-2 selective inhibitors are prompting research aimed at identifying other specific targets downstream of COX-2. In this regard, several groups have found that NSAIDs and COX-2 selective inhibitors primarily reduce the production of prostaglandin (PG) E₂, a biologically active lipid product of the COX-2 enzyme, which results in attenuation of PGE₂ signaling in the tumor microenvironment. Therefore, a detailed understanding of the PGE ₂ signaling pathway in transformed cells is critical to help identify novel and safer targets for effective prevention and/or treatment of cancer. Here we review the recent advances in elucidating the molecular mechanisms by which PGE₂ promotes carcinogenesis.