Metastatic melanoma is a complex illness that has inspired the development of both targeted treatment and immunotherapy. KIT-mutated melanoma is an uncommon subtype that often arises from acral, mucosal, or sun-damaged skin. KIT mutations are also more common in the triple wild-type subtype of cutaneous melanoma.
Activating mutations in KIT, a transmembrane receptor tyrosine kinase involved in cell formation, proliferation, and differentiation, have been linked to oncogenesis in a variety of tumor forms. Following the success of BRAF-targeted therapy in melanoma and KIT-targeted therapy in gastrointestinal stromal tumors, small-molecule tyrosine kinase inhibitors targeting KIT have been studied in melanoma with KIT mutation. Imatinib, sunitinib, dasatinib, and nilotinib are KIT inhibitors that have been studied in relevant clinical studies in metastatic melanoma. In these trials, individuals with KIT-mutated melanoma were demonstrated to be receptive to KIT inhibitor treatment, particularly those with L576P and K642E mutations.
As a result, KIT-targeted treatment has been included in the National Comprehensive Cancer Network recommendations for systemic therapy for metastatic or unresectable melanoma. Novel KIT-targeted treatments are currently being developed, as are KIT inhibitors in conjunction with immunotherapy.
Reference:link.springer.com/article/10.1007/s40257-018-0414-1
