Study on the cyclooxygenase-2 (COX-2) inhibitor Celecoxib in Skin Cancer

The Department of Dermatology is embarking on a study to test the hypothesis that the cyclooxygenase-2 (COX-2) inhibitor Celecoxib, administered orally over a period of 24 months, will prevent the development of basal cell carcinomas (BCCs) in patients with the nevoid basal cell carcinoma syndrome (BCNS).

Because of the increasing incidence of non-melanoma skin cancers (NMSCs) in the United States, there is great interest in identifying non-toxic drugs that can be employed for cancer chemoprevention. Patients with Nevoid Basal Cell Carcinomas (NBCC) are an attractive group for such a study because they develop large numbers of BCCs, thus allowing direct assessment of the effect of the agent on the cancers themselves. Indeed, a decade ago several investigators demonstrated that systemic retinoids can greatly reduce the development of new BCCs in such patients. Recent work indicates that a majority of patients with NBCCs and sporadic BCCs have a mutation in a gene known as Patched. The mechanism whereby Patched mutations result in increased BCCs remains to be explained.

The successful development of chemoprevention strategies can have benefits at several levels. The demonstration of a practical, well-tolerated agent that reduces the development of new BCCs would enhance the quality of life of patients with NBCCs. Furthermore, it is likely that chemopreventive agents that prove helpful in this small population also would be useful in the much larger population of individuals prone to the development of sporadic BCCs. Finally, the extent to which other abnormalities in patients with NBCCs are driven by the same molecular abnormalities is uncertain.

The NCI-funded study is a collaborative effort between Dr. David R. Bickers and Dr. Matthew Stiller in the Department of Dermatology here at NewYork-Presbyterian Columbia Campus, and Dr. Ervin Epstein at the University of California San Francisco.

Drs. Bickers and Stiller are also conducting a similar study to evaluate the potential of Celecoxib to provide photoprotection in human subjects exposed to ultraviolet radiation (UVR). In this study, Celecoxib will be administered to normal subjects and the effect of the drug on UVR-induced erythema (sunburn) examined. The goal is to expand and refine chemopreventive strategies to decrease the incidence of non-melanoma skin cancer and to determine whether Celecoxib can decrease UVR-induced erythema, and whether it can affect surrogate biomarkers of potential neoplastic change in UVR-exposed skin. The ability of Celecoxib to decrease the risk of skin cancer will be assessed by evaluating its ability to decrease sensitivity to UVR by periodic measurement of surrogate markers of carcinogenic insult in these subjects.