The purpose of this study is to review the development of BRAF inhibitors, with 
emphasis on the trials conducted with dabrafenib (GSK2118436) and the evolving 
role of dabrafenib in treatment for melanoma patients. Fifty percent of 
cutaneous melanomas have mutations in BRAF, resulting in elevated activity of 
the mitogen-activated protein kinase signaling pathway. Dabrafenib inhibits the 
mutant BRAF (BRAF(mut)) protein in melanomas with BRAF(V600E) and BRAF(V600K) 
genotypes. BRAF(V600E) metastatic melanoma patients who receive dabrafenib 
treatment exhibit high clinical response rates and compared with dacarbazine 
chemotherapy, progression-free survival. Efficacy has also been demonstrated in 
BRAF(V600K) patients and in those with brain metastases. Dabrafenib has a 
generally mild and manageable toxicity profile. Cutaneous squamous cell 
carcinomas and pyrexia are the most significant adverse effects. Dabrafenib 
appears similar to vemurafenib with regard to efficacy but it is associated with 
less toxicity. It is expected that new combinations of targeted drugs, such as 
the combination of dabrafenib and trametinib (GSK1120212, a MEK inhibitor), will 
provide higher response rates and more durable clinical benefit than dabrafenib 
monotherapy.