From the Editors

While great advances continue to be made in the treatment of skin cancer, prevention will always remain the best form of “cure.” With one in five Americans developing the disease, incidence still rising and often exorbitant costs involved in management (especially for advanced cancers), the need for effective chemopreventive agents has never been clearer.

Some of these agents, such as sunscreen ingredients, function as primary preventives, by blocking the DNA damage that can initiate carcinogenesis, while others inhibit, reverse or retard the progression of premalignant cells in which damage has already occurred. Ideally, they should be easy to administer, low-cost, have a proven mechanism of action and have few to no side effects.

To date, considerable research has focused on using vitamins and phytochemicals as antioxidants to combat oxidative stress. Vitamins E and C, polyphenols in green tea, silymarin in artichokes, curcumin in turmeric, lycopenes in tomatoes, resveratrol in grapes, gingerol in ginger, genistein in soybeans and beta-carotene in yellow vegetables are all known antioxidants that may lower the risk of cancer development. The prevailing view is that by destroying free radicals (highly reactive, damaging cells generated by natural internal processes or external insults such as UV), antioxidants can help to prevent mutations leading to cancer. Despite all the research, however, the effectiveness of antioxidants has not been definitively proven.

New forms of chemoprevention have emerged. For example, certain chemicals such as oral retinoids, derivatives of vitamin A, are now believed to help prevent skin cancer by defusing proliferation through cellular differentiation. The treatment can entail serious side effects, however.

Yet another intriguing new method of chemoprevention, one with a good safety profile and few side effects, involves enhancing the body’s ability to repair UV-induced DNA damage. The first significant examples of this kind of chemopreventive were liposomes containing the DNA repair enzyme T4N5, shown to reduce the immunosuppressive effects of UV exposure. And in the past year, research led by Dr. Diona Damian in Australia has revealed that nicotinamide, a version of vitamin B3 and an essential cofactor in ATP production, can significantly reduce recurrences of actinic keratosis, basal cell carcinoma and squamous cell carcinoma in patients with a history of these lesions.

In this issue of The Melanoma Letter, Dr. Damian and her coauthors Andrew Martin and Gary Halliday share their insights about how nicotinamide works. They have observed that both oral and topical nicotinamide replenish cellular ATP levels in human keratinocytes after the highly energy-intensive DNA repair processes triggered by both UV exposure and normal metabolism deplete them. They surmise that this energy-replenishing effect is a key mechanism by which nicotinamide reduces UV-induced immunosuppression and enhances DNA repair.

Dr. Damian and colleagues’ preclinical research suggests that nicotinamide may produce similar beneficial results in melanoma patients. The authors consider these early findings promising enough to recommend proceeding to clinical trials, especially with immunocompromised individuals and those with a substantial history of skin cancer, who to date have benefited most from nicotinamide treatment.

In this era when so much excitement has been generated by therapies that are exponentially increasing the lifespan of skin cancer patients with advanced disease, we should be every bit as enthused at the prospects of keeping high-risk patients from ever having advanced disease.

Allan C. Halpern, MD • Editor-in-Chief       

Ashfaq A. Marghoob, MD • Associate Editor