Epithelial Skin Cancer

Skin Cancer Research Has Helped Define the Biology of Cancer Pathogenesis

Epithelial nonmelanoma skin cancer (NMSC, primarily basal cell and squamous cell carcinoma) is the most frequent cancer among white populations, with incidence rates matching all other cancers combined in these groups. Although not frequently lethal, epithelial skin cancers are the cause of considerable morbidity, cosmetic defects, and extreme medical expense. Exposure to mutagenic ultraviolet (UV) light is the major skin carcinogenetic stimulus, but sun avoidance has often been superseded by lifestyle choices, and changing atmospheric conditions favor increased intensity of exposure. Thus, considerable attention has been directed to understanding the molecular pathogenesis of epithelial cutaneous cancer, and much progress has been achieved. Consequently, effective therapeutic approaches are evolving that have the potential to sharply reduce the morbidity and expense associated with these lesions. Skin cancer research has also provided significant insight into the mechanisms of understanding cancer pathogenesis in general. Centuries ago, astute clinicians and basic scientists first observed that chemical and physical exposures could cause skin cancer in humans and animals. Modern analysis of skin cancer induction demonstrated that cancers evolve from multiple, clonal, precancerous stages (initiation, promotion, premalignant progression, malignant conversion), and that genetic (e.g., mutation), epigenetic (e.g., gene expression or protein modification), and microenvironmental changes (e.g., inflammation, wounding) contribute to tumor formation. Skin studies first revealed that chemical carcinogens bind covalently to DNA, causing specific mutations in oncogenes and suppressor genes, and that DNA repair protects against cancer risk. In addition, cutaneous cancer research has indicated that viruses can cause human tumors; that immunosuppressed patients are susceptible to cancer; that genetic background can modify cancer rates; that diet, UV exposure, and cigarette smoke are cancer risk factors; and that signaling pathways initially associated with familial basal cell carcinoma (BCC) contribute to the pathogenesis of a variety of epithelial cancers of internal organs. Thus, epithelial skin cancer research has been a major contributor to defining cancer biology and biochemistry in general.