COX-2 as a target for cancer chemotherapy

Cyclooxygenase-1 and -2 (COX-1/2) catalyze the initial step in the formation of prostaglandins. Very recently their role in carcinogenesis has become more evident. They influence apoptosis, angiogenesis, and invasion, and play a key role in the production of carcinogens. Usually, a high level of COX-2 expression is found in cancer cells. Large epidemiological trials studying users and non-users of aspirin have shown that cyclooxygenase inhibitors and non-steroidal anti-inflammatory drugs (NSAIDs) could be of benefit against the development and growth of malignancies. Moreover, clinical trials in patients with familial adenomatosis polyposis syndrome have shown the efficacy of selective COX-2 inhibitors in the reduction of the number and size of colorectal polyps. Several preclinical studies show promising results with combinatorial treatments of either chemotherapy or radiotherapy with COX inhibitors. Preclinical studies with the simultaneous use of inhibitors of the epidermal growth factor receptor and COX-2 inhibitors have shown also promising results. Encouraging results from the first clinical trials combining chemotherapy with COX-2 inhibitors in patients with cancer in the advanced and neoadjuvant setting have recently been reported. Thus, it appears that targeting the COX-2 pathway is a promising strategy in the prevention and treatment of solid tumors.