Another Option in Our KIT of Effective Therapies for Advanced Melanoma

“Hodi et al reported the final results of a multicenter phase II trial of imatinib in patients with advanced melanoma harboring mutations or amplification of the KIT proto-oncogene. KIT is a transmembrane receptor tyrosine kinase, normally expressed on melanocytes, that plays a critical role in melanocyte migration, survival, proliferation, and differentiation. Mutations and amplification of KIT have been identified in melanomas arising from mucosal, acral or chronically sun-damaged surfaces, and they characterize a distinct genetic subset of disease. The alterations identified are, in most instances, mutually exclusive of BRAF and NRAS mutations and lead to constitutive activation of downstream signaling pathways including the MAPK, PI3K/AKT, and JAK/STAT pathways.”