SNOWMASS, COLO. — Skin tumors and their precursors possess potentially attractive targets for chemoprevention, and many are being actively investigated, according to David R. Bickers, M.D.
Exposure to UV light causes mutations in several tumor suppressor genes and increases the risk of skin cancer. That relationship makes methods of augmenting these genes a “tantalizing” prospect for skin cancer chemoprevention, he said at a clinical dermatology seminar sponsored by Medicis.
Topical cyclopamine, topical tazarotene, and topical antioxidants all hold promise, said Dr. Bickers, professor and chair of the department of dermatology at Columbia University, New York.
In addition, cyclooxygenase overexpression is a feature in some human neoplasms, which could point to COX-2 inhibitors as possibly chemoprotective, he added.
Dr. Bickers is also planning a trial of the retinoid tazarotene, which is another potentially chemopreventive agent.
Tazarotene upregulates a tumor suppressor known as tazarotene-induced gene 3 (TIG3) in human keratinocytes. That gene is diminished in patients with basal cell carcinoma (BCC), he explained.
One recent study found that topical treatment of BCCs with tazarotene increased TIG3 expression, resulting in both clinical and histological improvement (J. Invest. Dermatol. 2003;121:902-9).
Cyclopamine, a veratrum alkaloid, also has similar potential to inhibit BCCs, he said.
His work with mice showed that treatment with oral cyclopamine diminished tumor development, he explained. In addition, one human study of topical cyclopamine showed rapid regression of skin tumors and histologic evidence of tumor cell inhibition and apoptosis.
Finally, a very recent study of oral antioxidants has shown that sun exposure results in less DNA damage in patients who have taken a 3-month course of oral ascorbic acid (vitamin C) and alpha tocopherol (vitamin E), said Dr. Bickers (J. Invest. Dermatol. 2005; 124:304-7).
Similarly, another study found that oral antioxidant treatment with Polypodium leucotomos extract reduced sun-induced skin erythema (J. Am. Acad. Dermatol. 2004;51:910-8).
“While these results are modest, this strategy may prove more feasible as more potent compounds are developed,” he said.