Melanoma: Molecular Classification and Therapy

Abstract

Since the original classification and detailed histomorphological description of cutaneous melanoma, no major advancement has been made in the treatment of advance stages of this lethal disease. This chapter offers a brief review of the classic melanoma subtypes as described by Dr. Wallace Clark in correlation with the emerging melanoma types. Emphasis is given on the molecular types of melanoma, based on driver mutations found in many of the different melanoma groups. The most important mutations are alterations of molecular pathways involved in cellular proliferation, ultimately leading to tumor survival, growth, and metastases. These mutations include point mutations in BRAF, NRAS, and GNAQ/GNA11, as well as alterations of KIT. Capitalizing on the discovery of these molecular findings, prominent clinicians and researchers, in collaboration with the pharmaceutical industry, set up to rapidly develop drugs that are specific inhibitors of the effects of these mutations. These drugs include BRAF inhibitors, MEK inhibitors, and Kit inhibitors. These new therapies are described highlighting the fact that, although prolonging patient survival, they ultimately fail to control the spread of disease. However combination therapy between these kinase inhibitors and between kinase inhibitors and immunotherapy offers encouraging results and ought to be further studied and developed.