PGE2 plays a key role in colon carcinogenesis. Evidence continues to accumulate that cyclooxygenase-2 (COX-2), an inducible COX isoform, represents a potential pharmacological target for the prevention and treatment of cancer, including tumors affecting the large bowels. Several mechanisms of COX-2 related tumor promotion have been identified. Some are dependent on PGE2 production (such as induction of cell proliferation, angiogenesis or local immunosuppression, inhibition of apoptosis, increase in cell motility). COX-2 expression has been demonstrated in epithelial cells of colorectal cancers and adenomas. Studies in experimental models of colon carcinogenesis show that selective COX-1 or COX-2 inhibitors reduce tumor formation and growth. Clinical studies have been initiated to determine the chemoprotective effects of selective COX-2 inhibitors in patients with familial adenomatous polyposis or sporadic adenoma. Possible cardiovascular effects will need to be taken into account in an assessment of the potential ability of any of these drugs to prevent neoplasia in the large bowel and other organs. Based on the fact that PGE2 is involved in almost all events concerning carcinogenesis, further examinations concerning mPGES-1, EP receptors, and 15-PGDH, should be promoted as a target for colon cancer prevention and therapeutics. Hence, detailed analyses are needed to clarify PGE2 related carcinogenesis.
2007 by The Japanese Society of Strategies for Cancer Research and Therapy