Celebrex combats skin cancer in vulnerable group

Anti-inflammatory drug limits tumors in patients with hereditary condition

The inflammation-fighting drug celecoxib prevents some outbreaks of skin cancer in people genetically predisposed to developing the malignancy, scientists report in the January Cancer Prevention Research.

People with a rare hereditary condition called Gorlin syndrome develop hundreds or even thousands of basal cell carcinomas in a lifetime. This predisposition stems from having an abnormal version of the PTCH1 gene which normally provides blueprints for a protein that helps to keep cell growth in check. The mutated PTCH1 gene results in a nonfunctional protein, removing a key obstacle for skin cancer.

Celecoxib, marketed as Celebrex, is a nonsteroidal anti-inflammatory drug. Other NSAIDs — including ibuprofen, aspirin and naproxen — suppress inflammation-causing enzymes called cyclo-oxygenase 1 and 2, but celecoxib inhibits mainly COX-2. Past research suggested that these COX inhibitors also have anticancer effects, and earlier tests in mice had shown that celecoxib itself thwarted another skin cancer, called squamous cell carcinoma.

The COX enzymes contribute to new blood vessel growth, which tumors need to survive, says dermatologist Jack Arbiser of Emory University in Atlanta.

In the new study, researchers tested mice lacking a functional PTCH1 gene and found that when exposed to ultraviolet light, these animals developed basal cell carcinoma. Celecoxib added to the animals’ chow reduced the cancer by one-third.

The researchers then recruited 60 people with Gorlin syndrome and randomly assigned 33 to get celecoxib and 27 to get placebo pills. Over the next two years, people with mild Gorlin syndrome — defined as fewer than 15 skin cancer lesions at the study’s start — fared better if they got the drug. They had fewer than half as many new cancerous lesions and about half as much skin area covered with cancerous growths as did those getting placebo pills.

Patients entering the study with 15 or more cancer spots didn’t benefit from celecoxib. “Those with a lot of lesions may have other genetic mutations that make their cancer more robust,” says study coauthor Jean Tang, a dermatologist who worked on the study while at the University of California, San Francisco. She is now at Stanford University.

Basal cell carcinoma is the most common malignancy in humans, with roughly 1 million new cases each year in the United States. While people with mild Gorlin syndrome benefited from celecoxib in this study, the condition is rare. A study of skin cancer in people taking ibuprofen might shed light on the value of that NSAID for preventing skin cancer in the general population, Arbiser says.

For now, Arbiser doesn’t think NSAIDs should be recommended broadly for people at high risk of skin cancer — anyone with a lot of sun exposure — because of previous questions raised about side effects of certain potent COX-2 inhibitors. Two such drugs, Vioxx and Bextra, were pulled off the market several years ago when side effects emerged that included heart problems. Celecoxib, a milder drug, remains in use. In this study, no one taking the drug had cardiac symptoms.

Medical oncologist Charles Rudin of the Johns Hopkins Kimmel Cancer Center in Baltimore says COX inhibitors might someday play a role in fighting skin cancer, but probably only in combination with other drugs. In 2009, Rudin and his colleagues published data from patients with basal cell carcinoma indicating that an experimental drug made by Genentech called GDC-0449, also inhibited this skin cancer.

For people at risk of basal cell carcinoma, the use of drugs as topical creams might ultimately prove most useful, Rudin says.

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