B-RAF: A contributor to the melanoma phenotype

B-RAF, a serine-threonine protein kinase, is one of the three RAF paralogs in humans. B-RAF participates in the RAS-RAF-MEK-ERK pathway, a conserved protein kinase-signalling cascade that is involved in regulating a number of critical cellular functions. Mutated B-RAF is believed to play a crucial role in the development, maintenance and progression of melanoma, where it contributes to multiple aspects of the malignant phenotype, such as cell survival, proliferation and apoptosis resistance. Indeed, it is mutated in a high proportion of melanocytic skin lesions and B-RAF mutations are preserved through melanoma progression. Despite this, the direct inhibition of B-RAF has shown little success clinically in the treatment of melanoma, presumably due to the complexity of the RAS-RAF-MEK-ERK pathway. For this reason, alternative strategies must be developed to treat oncogenic B-RAF-induced melanomas. (C) 2010 Elsevier Ltd. All rights reserved.