Critical Reviews in Oncology/Hematology 41 (2002) 269– 285 www.elsevier.com/locate/critrevonc Chemoprevention of human skin cancer Janine G. Einspahr *, Steven P. Stratton, G. Timothy Bowden, David S. Alberts Arizona Cancer Center, Uni6ersity of Arizona, 1515, North Campbell A6enue Tucson, AZ 85724, USA Accepted 2 July 2001 Contents 1. Background . . . . . . . . . . . . . . . . . . . . . . . . . 1.1. Impact of skin cancer . . . . . . . . . . . . . . . . 1.2. Incidence of AK and relationship to SCC . . . . 1.3. Clinical and histologic features of AK and SCC 2. Sunlight as a carcinogen . . . . . . . . . . . . . . . . . . . . . 2.1. Ultraviolet (UV)-induced DNA damage . . . . . . . . 2.2. p53 gene response to UV-induced DNA damage . . . 2.3. p53 mutations in UV-induced carcinogenesis . . . . . 2.4. UV-induced alterations in second messenger systems . (SEBs). 4. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Reviewers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Biography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3. Skin cancer chemoprevention . . . . . . . . . . . . . . . . . . . Cancer chemoprevention and use of surrogate endpoint Chemopreventive agents and molecular targets . . . . . Human chemoprevention studies in NMSC . . . . . . . biomarkers Abstract The incidence of skin cancer has been rising in recent years with significant effects on public health. Primary prevention has proven inadequate in impacting the incidence of skin cancer, thus stimulating the development of chemopreventive strategies. The majority of skin cancer chemoprevention studies focus on occurrence of new nonmelanoma skin cancers (NMSC) in individuals with a previous NMSC, or on reduction in the number of premalignant skin lesions such as actinic keratoses (AK). Dysplastic nevi, a likely precursor of melanoma, are also potential targets for chemoprevention strategies. Premalignant lesions are especially attractive as endpoints since they are more common than frank cancer, resulting in reduced sample size, length, and cost of clinical trials. Development of new agents that affect the pathogenesis of skin cancer will be discussed, from elucidation of molecular targets to implementation of trials designed to determine the effects of chemopreventive interventions on human skin cancer. © 2002 Elsevier Science Ireland Ltd. All rights reserved. * Corresponding author. Tel.: + 1-520-626-2444; fax: + 1-520-626-2735. E-mail address : jeinspahr@azcc.arizona.edu (J.G. Einspahr). 1040-8428/02/$ - see front matter © 2002 Elsevier Science Ireland Ltd. All rights reserved. PII: S 1 0 4 0 - 8 4 2 8 ( 0 1 ) 0 0 1 8 5 - 8