Optimal Selection of Targeted Therapies for Melanoma Patients: Role of the Mitogen-Activated Protein Kinase Pathway

Advances in our understanding of immune checkpoints and the mitogen-activated protein kinase pathway (MAPK) have driven substantial improvements in systemic treatments for melanoma. The MAPK pathway is a key oncogenic signaling system which drives melanoma metastasis, proliferation, and survival. The discovery of BRAF V600 mutations which are found in 40-50% of cutaneous melanoma has led to the development of selective inhibitors such as vemurafenib and dabrafenib. Drugs targeting MEK that synergistically inhibit the MAPK pathway complement BRAF inhibitors. Combinations of BRAF and MEK inhibitors are now the standard of care for BRAF V600-mutated melanoma. Other molecular targets commonly identified in melanoma include NRAS and KIT mutations that may open up other therapeutic avenues. Further research into these oncogenic targets is needed to build on the recent advances in melanoma systemic treatment. This chapter discusses the importance of the MAPK pathway and its place in the evolving treatment landscape of melanoma.