Targeted Therapies in Melanoma: Knowledge, Resistance and Perspectives

Abstract

Several molecular mechanism appear to play a major role in melanoma genesis and progression. Current targeted therapies focus on contrasting the activation of RAS/RAF/MEK/ERK and, to a less extent, PI3K/AKT pathways. Development of inhibitors of key effectors (mainly, BRAF mutant and MEK) has significantly improved treatment of patients with advanced melanoma. However, only rarely tumours present a durable regression due to a large variety of acquired and intrinsic mechanisms that drive resistance to the main targeted inhibitors. All these evidence suggest that in melanoma, as probably in all types of cancer, use of a combinatorial treatment approach, instead of targeting a single component of melanomagenesis pathways, could delay or prevent the emergence of resistance mechanisms responsible to tumour relapse. In this sense, a crucial step is thus represented by the full knowledge of such molecular mechanisms.