Dr. Paul Lizzul and Dr. Allan Conney, along with their colleagues, are in the early stages of research that hints at broad implications for preventing squamous cell and basal cell skin cancer. After starting in the lab and progressing with animal models, they took a hypothesis about the effect of caffeine on actinic keratoses and applied it to humans in a recent phase I study. They shared some thoughts on this research with the Skin & Allergy News blog, the Mole:
The Mole: What prompted you to conduct this study?
Dr. Lizzul: Skin cancer of the nonmelanoma type (i.e., squamous cell and basal cell carcinoma) is the most common skin cancer and is most often a result of sunlight exposure. Ultraviolet B light is believed to be mostly responsible for these cancers. Many squamous cell skin cancers are curable if detected early. However, many people still suffer from these cancers and some also die from them. Actinic keratoses are precancerous skin tumors that mainly result from long-term sun exposure in susceptible persons. They have the potential to progress to squamous cell carcinoma. Finding effective methods of preventing UV-induced cancers and precancerous lesions would have a major impact on the total amount of human cancer.
The Mole: Could you briefly explain your hypothesis?
Dr. Conney: In studying the effect of tea on UVB carcinogenesisis in an animal model, we found that caffeine was the major active constituent, and that pure caffeine inhibited carcinogenesis in this animal model. Topical caffeine was also active. Topical caffeine inhibited carcinogenesis in mice pretreated with UVB with a high risk of skin cancer in the absence of further UVB. Mechanistic studies showed that caffeine enhanced apoptosis (programmed cell death) in UVB-treated epidermis and in tumors. We hypothesize that topical caffeine will inhibit proliferation and stimulate apoptosis in the actinic keratoses.
Dr. Lizzul: The hypothesis to be tested in this study is that treatment of actinic keratoses with caffeine for 2 weeks will enhance apoptosis and inhibit the growth of these skin lesions in humans. The purpose of this study is to determine the effects of topical applications of caffeine on apoptosis (programmed cell death), proliferation, and the ATR/Chk1 pathway in actinic keratoses in human skin in vivo.
Our collaborators at Rutgers University found that treatment of UVB-pretreated high-risk mice with caffeine topically once a day, 5 days a week for 18 weeks inhibited the formation of keratoacanthomas and squamous cell carcinomas, decreased the size of the tumors, and enhanced apoptosis in the tumor.
At Rutgers University, Drs. Yaoping Lu, Yourong Lu, and Allan Conney are participating in the study.
—Heidi Splete (on Twitter @hsplete)