Basal cell carcinoma and squamous cell carcinoma are the most frequent types of 
cancer in the United States and represent 75 percent and 20 percent, 
respectively, of all nonmelanoma skin cancers. Since ultraviolet radiation is 
implicated in their development, photoprotection is fundamental in their 
prevention. Additional preventive measures include identifying high-risk 
individuals for early detection along with using agents, such as retinoids, that 
are effective in decreasing the risk of premalignant cells further developing 
into carcinomas. Newer agents achieving this goal include perillyl alcohol, T4 
endonuclease 5, DL-alpha-tocopherol, and alpha-difluoromethylornithine. 
Procedural modalities are currently the standard of treatment, but recent 
evidence has consistently shown that newer (nonsurgical) therapies, such as 
interferon, imiquimod, retinoids, and 5-fluorouracil, can be used effectively 
either as monotherapies or as adjuvants to those surgical modalities for the 
treatment of superficial nonmelanoma skin cancers and premalignant lesions. 
These newer therapies have achieved significant reductions in morbidity and 
mortality. Procedural modalities that have been evolving into important tools 
for the treatment of actinic keratosis and nonmelanoma skin cancers include 
photodynamic therapy and lasers. Nonsurgical therapies currently proving to be 
effective in clinical trials include ingenol mebutate and cyclooxygenase-2 
inhibitors. Agents that are showing promising results in early phases of 
clinical trials include betulinic acid; hedgehog signaling pathway inhibitors, 
such as cyclopamine and GDC-0449; alpha-melanocyte-stimulating hormone analogs, 
such as afamelanotide; epidermal growth factor receptor inhibitors, such as 
gefitinib and erlotinib; anti-epidermal growth factor receptor monoclonal 
antibodies, such as cetuximab and panitumumab; and the 5-fluorouracil prodrug 
capecitabine.