40 million people worldwide rely on daily doses of NSAID to treat the pain and inflammation of arthritis, about 25% develop ulcers. This is related to significant mortality largely due to NSAID-related gastrointestinal bleeds. The risk of gastrointestinal side effects resulting from NSAID use increases with age - unfortunately so does the use of this class of analgesia. A number of strategies have therefore been adopted to overcome the gastrointestinal toxicity of NSAIDS. The most well documented in recent years has centered on the development of COX-2 specific inhibitors and currently at least 30 molecules are in development or on the market. More recently, this pharmacological class has been shown to have anti-cancer properties and as a result Celecoxib has been launched as a treatment for polyps, a premalignant form of colon cancer. A number of COX-2 inhibitors are now in development for various forms of cancer. Although a number of types of cancer such as primary breast cancer and prostate cancer can often be treated successfully, as with most cancers, metastatic disease is not usually curable. The development of therapeutic strategies for the prevention and treatment of metastatic cancers thus represents a key priority for the pharmaceutical industry. It is therefore of interest that researchers based in Ireland have recently shown that the COX-2 inhibitor, SC-236, as well as the non-selective COX inhibitor, indomethacin reduced primary tumor weight and the number of lung metastases in a model of advanced breast cancer. Decrease in microvessel density and VEGF production as well as an increase in tumor cell apoptosis in the primary tumor mirrored these findings. Although the therapeutic activity of COX inhibitors has previously been demonstrated in breast cancer this study is one of the first to demonstrate that this is related to angiogenesis and apoptosis, two highly promising areas of anti-cancer therapy. These data and previous report suggesting that COX inhibitors reduce the invasiveness of breast cancer cells adds weight to the concept of developing COX inhibitors for the treatment of neoplastic diseases such as breast cancer.

Entry date September, 2002

Adapted from Connolly et al, Br J Cancer 2002 Jul 15;87(2):231-7

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