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LEARNING OBJECTIVES
Upon completion of the chapter, the reader will be able to:
Identify the risk factors associated with skin cancer.
Devise a plan of lifestyle modifications for the prevention of skin cancer.
Discuss the importance of mutation testing in the therapy selection for melanoma treatment.
Explain the goals of therapy for the treatment of different nonmelanoma and melanoma stages.
Compare and contrast the available pharmacologic treatment options for nonmelanoma and melanoma skin cancer.
Suggest management strategies for patients experiencing adverse effects of pharmacologic therapy.
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Skin cancer is the most common malignancy in the United States with over 5 million new diagnoses reported in roughly 3 million individuals. Of these, more than 95% are diagnosed with nonmelanoma skin cancer (NMSC), while the rest of skin cancer diagnoses are accounted for by malignant melanoma (MM).1,2 NMSC incidence increased 300% since 1994 and continues to rise due to increasing high-risk populations, such as organ transplant and photosensitizing medication users. NMSC consists of basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs), which originate in the basal cell layer and the hair follicle stem cells, respectively.3 MM differs substantially from NMSC with regard to its metastatic potential, prognosis, and treatment options.
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EPIDEMIOLOGY AND ETIOLOGY
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MM is the most diagnosed malignancy in young adults and the fifth most frequently diagnosed cancer overall in the United States, representing approximately 5% of all cancer cases. Although accounting for less than 3% of the skin cancer diagnoses, MM is responsible for the majority of skin cancer deaths (75%).1,4 With a median age at diagnosis of 65, approximately half of MM cases are diagnosed between ages 55 and 74. An estimated 106,110 new cases are predicted to occur in 2021.5 However, these figures may underestimate MM, since many superficial and in situ melanomas are treated in outpatient settings and thus not included in the Surveillance, Epidemiology, and End Results (SEER) registry.
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MM risk factors include environmental and host factors. 
Sun exposure and ultraviolet (UV)-based artificial tanning are the main environmental triggers for melanoma occurrence. Residing in sunnier climates closer to the equator with potential for chronic sun exposure also increases the risk of melanoma. While MM can occur in any ethnic group and also on less exposed areas of the body, individuals of fair complexion (fair hair and light-colored eyes) have an increased risk.5 Furthermore, individuals with genetic susceptibility may develop exacerbated skin reactions to the sun or UV radiation (UVR), particularly UVB. While UVB exposure is a well-known risk factor, the most common genetic lesions induced by UVB are C to T conversions, while the most common melanoma associated mutations are BRAF V600E and NRAS Q61L, which are unlikely to be caused by UVB....