Emerging growth factor receptor antagonists for the treatment of advanced melanoma.

INTRODUCTION: Therapy for metastatic melanoma has undergone a rapid transformation over the past 5-10 years. Advances in immunotherapy with checkpoint inhibitors, including both anti-CTLA-4 and anti-PD-1/PD-L1, have led to durable responses in up to 50% of patients. As our understanding of the processes driving the transformation of melanocytes has improved, progress in targeted therapies has also continued. Areas covered: Angiogenesis and the tumor's dependence on an expanded vascular supply has been a target for novel therapies since the 1970's, as this tissue is derived from endothelial cells that are genetically stable in adults. A phase II trial studying combined therapy with bevacizumab (an inhibitor of angiogenesis) and ipilimumab found promising results. Other agents such as sorafenib have not been as successful, failing to extend progression free or overall survival in clinical trials. In this paper other targeted growth factor inhibitors will also be discussed. Expert opinion: Ultimately, melanoma may not be vulnerable solely to chemotherapy or targeted therapy, but may be efficaciously treated with immunotherapy due to its high mutational rate resulting in the expression of numerous neo-antigens. Therapies with combinations of agents including growth factor receptor and either other targeted therapies or immunotherapy may be a promising complimentary approach.