New Recommendation for Melanomas with KIT Mutations

Thanks partly to a new study, national guidelines now include a targeted treatment for melanomas with mutated KIT genes. The drug, called imatinib, is already used for chronic myelogenous leukemia. In a phase II clinical trial that included 12 people with melanomas that had KIT mutations, imatinib shrank tumors in 77%. KIT abnormalities can also include too many copies of this gene, but the drug was not effective against these tumors. KIT mutations, which are relatively uncommon, can occur in mucus membranes, extremities such as fingers, and skin with chronic sun damage. Now that there is a recommended targeted treatment, the researchers advise testing such melanomas for KIT mutations.

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.”

KIT-Mutated Melanomas Respond to Imatinib

“Imatinib has activity in KIT-mutated mucosal, acral, or chronically sun-damaged melanoma.”

Imatinib for Melanomas Harboring Mutationally Activated or Amplified KIT Arising on Mucosal, Acral, and Chronically Sun-Damaged Skin

“Amplifications and mutations in the KIT proto-oncogene in subsets of melanomas provide therapeutic opportunities…We conducted a multicenter phase II trial of imatinib in metastatic mucosal, acral, or chronically sun-damaged (CSD) melanoma with KIT amplifications and/or mutations…Melanomas that arise on mucosal, acral, or CSD skin should be assessed for KIT mutations. Imatinib can be effective when tumors harbor KIT mutations, but not if KIT is amplified only. NRAS mutations and KIT copy number gain may be mechanisms of therapeutic resistance to imatinib.

Determining the profiles and parameters for gene amplification testing of growth factor receptors in lung cancer

We attempt to establish appropriate conditions for standardization of the determination of gene amplification in a panel of growth factor receptors. We provide with parameters for the determination of gene amplification at ERBB2, MET, KIT, and PDGFRA which could be implemented in the clinic to stratify lung cancer patients for specific treatments