A critical turning point in the fight against advanced and metastatic melanomas occurred just over a decade ago with the discovery and characterization of the BRAF activating mutation V600E in about 60% of melanomas (Davies et al., 2002). This mutation causes constitutive activation of the B-Raf serine/threonine kinase, resulting in aberrant and persistent activation of the Raf-MEK-ERK mitogen-activated protein kinase cascade. Importantly, BRAF V600E correlated with poor prognosis in patients with metastatic melanoma. This prompted the development and clinical evaluation of Raf and MEK inhibitors for the treatment of BRAF mutant metastatic melanoma (Salama and Flaherty, 2013).
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