Nonsteroidal anti-inflammatory drugs in the prevention and treatment of colorectal cancer

Abstract

Numerous experimental, epidemiological and clinical studies suggest that non-steroidal anti-inflammatory drugs (NSAIDs) may exert anticancer activity. This effect may result from the inhibition of cyclooxygenase-2 (COX-2) activity and reduced production of prostaglandin E2, which has an important role in the pathogensis of inflammation and promotion/progression of human cancers. Many epidemiological studies have shown that long-term use of acetylosalicic acid reduced the incidence and mortality from colorectal cancer (CRC) and lowered the incidence of adenomatous polyps in the colon. In phase III studies, two selective COX-2 inhibitors, sulindac and celecoxib, were found to inhibit the growth of adenomatous polyps and cause regression of existing polyps in patients with familial adenomatous polyposis. A specific biomarker of acetylosalicylic acid anticancer activity in CRC may prove to bea mutation in PIK3CA gene. The chronic use of NSAIDs, especially selective COX-2 inhibitors, for CRC prevention is limited due to their side effects, in particular digestive tract bleeding. However, the development of new types of drugs and progress of molecular biology, will probably allow selection of best candidates for personalized NSAIDs chemoprevention of CRC and others malignancies.