The popular anti-inflammatory drug celecoxib, more commonly known as Celebrex, could significantly reduce the number skin cancer tumors among people who have a rare condition called Gorlin syndrome. Patients with this genetic condition are highly vulnerable to developing skin basal cell carcinoma, the most common type of skin cancer, and often experience hundreds or even thousands of these tumors over a lifetime.
Celecoxib is a non-steroidal anti-inflammatory drug (NSAID) differs from other NSAIDs in that it inhibits the inflammation-causing enzymes called cyclo-oxygenase 2 (COX-2), whereas other NSAIDs such as ibuprofen, aspirin, and naproxen inhibit mainly COX-1 enzymes. Previous research has shown celecoxib to have success in opposing squamous cell carcinoma, another type of skin cancer. In addition, other research has suggested that COX inhibitors in general can have anticancer effects.
According to Ervin H. Epstein, Jr., M.D., of Children's Hospital of Oakland Research Institute, and colleagues, the COX-2 inhibitor celecoxib may substantially decrease the vulnerability of Gorlin syndrome patients of developing basal cell carcinoma tumors. In a Phase II trial, the use of celecoxib in patients with Gorlin syndrome slowed the increase of tumors by 11 to 30 percent. These significant effects were seen in patients having less severe cases of the condition. A report on the findings was recently published in the American Association for Cancer Research’s journal Cancer Prevention Research.
Gorlin syndrome, also known as nevoid basal cell carcinoma syndrome, is a condition that affects multiple areas of the body, and increases the likelihood of developing various types of benign tumors. It is caused by a genetic mutation of the PTCH1 gene that is often inherited from one affected parent. Although the PTCH1 gene normally provides instructions for making a protein functions to keep cell growth in check, the mutated gene prevents production of the protein or results in an abnormal version.
During the initial study, mice that lacked a functional PTCH1 gene were found to develop basal cell carcinoma when exposed to ultraviolet light. However, when the mice were given celecoxib, cancerous lesion development was reduced by a third. In Phase II of the study, the researchers randomly assigned 60 people with Gorlin syndrome to receive either celecoxib or a placebo. The study subjects were followed over a two-year period.
Findings revealed that of the 33 participants who received celecoxib, those with mild Gorlin (defined as having less than 15 skin cancer tumors at the beginning of the study) experienced improvement. Compared to patients who received a placebo, these patients developed 50 percent less new cancerous lesions and only had about half as much skin area covered with tumors, meaning that those who did develop cancer tumors experienced less severe cases.
Other findings of the study showed that patients who started the study with more than 15 tumors did not benefit from receiving celecoxib. In addition, the study authors cautioned, “the potential cardiovascular risks associated with celecoxib would seem to preclude its widespread use.”
According to the National Institutes of Health, it is estimated that about 1 in 57,000 people have Gorlin syndrome. Of the more than 1 million new cases of basal cell carcinoma diagnosed each year in the United States, less than 1 percent of them are related to Gorlin syndrome.
