Therapeutic Implications of KIT in Melanoma

Melanoma is a heterogeneous disease representing distinct biologic and genetic subsets. Activating mutations in KIT have been discovered in a significant proportion of melanomas arising from acral, mucosal, and chronically sun-damaged sites and represent an important melanoma genetic subset. Initially, KIT was believed to function as a tumor suppressor, but additional research suggests that, in certain contexts, KIT functions as an oncogene. Therapeutic strategies targeting KIT with imatinib demonstrated remarkable efficacy in patients with gastrointestinal stromal tumors, but initial trials in melanoma were unsuccessful. Nevertheless, case reports continued to surface that demonstrated the remarkable efficacy of imatinib for patients with specific KIT genetic aberrations. Recently, trials of imatinib have selected patients with KIT genetic aberrations and have shown promising results. Current efforts are investigating additional agents that target KIT and testing KIT inhibitors in combination with other agents to improve the outcome for patients with this genetic subset of melanoma.