Introduction
tumor, melanoma
DISEASE, TUMOR, MELANOMA, METASTATIC MELANOMA
Immunotherapy and targeted therapy have demonstrated unprecedented efficacy and have significantly improved the outcome of patients with metastatic melanoma. The major advantage of immunotherapy (IT) is the long-term benefit even if the treatment is discontinued. The strength of targeted therapy (TT) is the immediate response of most patients treated that can ameliorate critical disease related symptoms in the individual patient. Based on these major differences between the two therapy types, there was the clear promise that the combination of both might keep the advantages of every single combination partner [The hypothesis of potential synergies of TT/IT combinations has been based on preclinical data, demonstrating that the activation of the mitogen-activated protein kinase (MAPK) pathway causes an immunosuppressive microenvironment including the presence of cytokines dimishing T-cell activity, decreased expression of melanoma differentiation antigens (MDA) and surface human leukocyte antigens class I (HLA-I). This results in reduced activity and functionality of tumor specific cytotoxic T cells [