Drug Discovery Opinion

Researchers in the US have shown that the COX-2 inhibitor, celecoxib, can slow the development of basal cell carcinoma. Although celecoxib was known to inhibit the development of squamous cell carcinoma in mice, and epidemiological studies had suggested a protective role in people, little was known about its efficacy in preventing the more common basal cell carcinoma. In mice with a genetic mutation similar to that which occurs in Gorin syndrome – a genetic condition which predisposes to basal cell carcinoma – deletion of the COX-1 or COX-2 gene reduced the microscopic tumour burden by 75% when the mice were exposed to ionising radiation. Treatment with celecoxib reduced the tumour burden by 35%. The overall size of the tumours was also shown to be doubled in mice engineered to overexpress COX-2.

In a planned 3-year, double-blinded, randomised clinical trial in 60 patients with Gorin syndrome, a trend towards reduced basal cell carcinoma burden was seen in all subjects receiving oral celecoxib (200mg bid). If only patients with less severe disease (less than 15 lesions at study entry) were included in the analysis, celecoxib significantly reduced basal cell carcinoma number and burden: subjects receiving placebo had a 50% increase in burden per year whereas subjects in the celecoxib group had a 20% increase. The study began recruiting in 2001 and was discontinued in 2004 when rofecoxib was withdrawn from the market amidst concerns about an association between long-term treatment with COX-2 inhibitors and increased incidence of heart attack and stroke. At that time, most patients had received celecoxib for 2 years and none had suffered cardiovascular side effects as a result of participation in the trial. Although safety concerns appear to preclude oral dosing, the researchers hope that topical application of celecoxib could provide safer, yet still effective, protection against basal cell carcinoma.

The study is published in the January issue of Cancer Prevention Research.

Epidemiological studies have also linked COX-2 inhibitor use to reduced incidence of other cancers, including colorectal cancer and breast cancer. Inhibition of the COX-2 pathway has been shown to reduce cancer cell proliferation, increase apoptosis and reduce angiogenesis, as well as modifying the immune response.

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