C-kit-mutated melanomas

Abstract

Malignant melanoma is the most frequent cause of mortality in skin cancer. Unlike Caucasians, mucosal and acral melanomas account for approximately 65% of all melanomas in Chinese. Genetic mutations of c-kit are detected in mucosal and acral melanomas, which thus can be regarded as molecular targets for treatments. This review describes the recent proceedings in the c-kit-targeted molecular therapy of melanoma, on the basis of our experiences in Chinese melanoma patients. Somatic mutations within c-kit gene have been detected in 10.8% of Chinese melanoma patients. Imatinib, a selective inhibitor targeting Abl as well as c-kit and the platelet-derived growth factor receptor, has been tested for the efficacy and toxicities in metastatic melanoma patients, suggesting that imatinib may increase the progression-free survival and overall survival in selected melanoma patients harboring mutations in c-kit gene. The current status of c-kit mutation and the standard for selection of imatinib-sensitive patients have been tentatively established. C-kit is a proto-oncogene that can serve as a potential target for molecular therapy of metastatic melanoma. Imatinib is effective and well tolerated in the treatment of metastatic melanoma patients. In selected subsets of melanoma patients harboring genetic alterations of c-kit, imatinib may be a promising agent.