Melanoma and Other Skin Cancers

Abstract

Skin cancers are the most prevalent of all malignancies with 50% of all Americans reaching the age of 65 expected to develop one form of skin cancer in their lifetimes. The two most common forms of skin cancer, basal cell carcinoma and squamous cell carcinoma (the so-called nonmelanoma skin cancers), develop from keratinocytes, have a low tendency to metastasize and are less deadly. In contrast, melanomas develop from melanocytes follow an aggressive clinical course and account for the majority of skin cancer deaths. The recent years have seen a giant leap in our understanding of the molecular events that underlie the development and progression of both melanoma and nonmelanoma skin cancers. This has in turn led to the development of targeted therapeutic agents that specifically inhibit the oncogenic mutations that drive these cancers. In this review, we outline the latest knowledge on the etiology, biomarkers, and prognostic classification of both melanoma and nonmelanoma skin cancers. We discuss in detail how the comprehensive genetic analysis of melanoma has led to a number of distinct molecular subgroups of melanoma being described and review the latest literature on the preclinical and clinical development of personalized therapy strategies for both melanoma and nonmelanoma skin cancers. We finally look to the future and describe how the in-depth mutational profiling of patients’ tumors will yield important diagnostic and prognostic information and help guide the choice of therapy.