Recent Progress in Mutation-driven Therapy, Immunotherapy and Combination Therapy for the Treatment of Melanoma

Abstract

With increases in our understanding of the human genome and immune system, the treatment armamentarium for melanoma has benefitted from the development and approval of BRAF inhibitors, MEK inhibitors, immune checkpoint modulators via cytotoxic T-lymphocyte antigen-4 blockade, and PD-1 and PD-L1 inhibitors. These advances, however, have raised questions about combination therapy, the optimal sequential use of these agents, the limited assessment of response using traditional metrics, and the optimal selection of the population to be treated. In this review we summarize recent breakthroughs and then itemize the development of newer agents, potential prognostic and predictive biomarkers, resistance mechanisms, and strategies of combination therapy. We also emphasize the multifaceted attributes of immunotherapy in terms of durable responses and longterm survival that paradoxically necessitate further research into the underlying mechanisms and longer patient follow-up.

Keywords: BRAF inhibitors; CTLA-4 inhibitors; MEK inhibitors; Melanoma; PD-1 inhibitors; PD-L1 inhibitors; immunotherapy; mutationdriven therapy.