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.