Melanoma Review: Background and Treatment

Eva Berrios-Colon, PharmD, MPH, BCPS; Shalonda Williams, PharmD


US Pharmacist 

In This Article

Etiology and Risk Factors

The etiology of melanoma is not fully understood, but many intrinsic and extrinsic factors have been identified that contribute to the occurrence of cutaneous melanoma. Physical characteristics such as blue or green eyes, red or blond hair, pale complexion, high degree of freckling, and tendency to sunburn put one at greater risk for developing melanoma. The number of melanocytic nevi on the body and the presence of atypical melanocytic nevi increase the risk of melanoma.[3]

Family history and personal history of melanoma are two important factors for diagnosis. If a patient has at least one family member who was diagnosed with melanoma, the risk of diagnosis increases 2.2-fold. The risk is 100% if the patient has two or more family members with dysplastic nevi and/or melanoma.[6] Immunosuppression is also a risk factor for melanoma. Maternal–fetal transfer of melanoma is rare but should be noted, as melanoma is the cancer most likely to metastasize from the placenta to the fetus. Congenital melanocytic nevi are also considered precursors for melanoma. External risk factors include geographic location and increased exposure to sunlight and UV radiation.[3]

Several gene mutations that relate to melanoma risk have been identified. Cyclin-dependent kinase inhibitor 2A and melanocortin-1 receptor gene have been associated with an increased risk of hereditary melanoma.[1] Familial atypical multiple mole melanoma syndrome (also known as dysplastic nevus syndrome), a hereditary disease that increases the risk of melanoma 400- to 1,000-fold, is characterized by a predisposition to develop dysplastic nevi and cutaneous melanoma.[3] The mitogen-activated protein kinase pathway is a major signaling pathway that has been associated with the development of melanoma. A high prevalence of BRAF gene mutations appears to be an epidemiologic link between UV radiation and melanoma. Alterations in melanoma-specific pathways such as NEDD9, MITF, and NRAS also play a role in the development of melanoma. Studies continue to explore the relationship between molecular genetics and melanoma risk in the hope of better understanding the disease and identifying new targets for pharmacologic therapy.[3]


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