RAF kinase inhibitors for the treatment of melanoma

Malignant melanoma is one of the most lethal solid tumors unless detected early. Malignant melanoma accounts for about 75% of skin cancer-related deaths. Around 68,700 cases of new melanoma were diagnosed in 2009 in the U.S. According to a World Health Organization report, about 48,000 melanoma-related deaths occur worldwide per year. In its early stages, melanoma can be treated surgically, leading to 5-year survival rates exceeding 90%. However, when it becomes metastatic, it is uniformly fatal, with 5-year survival rates of < 2% and a median survival of 6-10 months. Recent advances in the understanding of the molecular heterogeneity offer the promise of a better future for drug development in melanoma. The MAP kinase pathway is known to be associated with several human cancers, including malignant melanoma. The MAP kinase pathway is activated through mutations in BRAF, and BRAF V600E is the most common among these mutations. Targeted therapy involving B-raf inhibition was thought to yield promising results. This review provides information on various B-raf inhibitors and the clinical impact these drugs may have in patients with melanoma.