BRAF mutation predicts sensitivity to MEK inhibition

摘要: The kinase pathway comprising RAS, RAF, mitogen-activated protein (MEK) and extracellular signal regulated (ERK) is activated in most human tumours, often through gain-of-function mutations of RAS RAF family members. Using small-molecule inhibitors MEK an integrated genetic pharmacologic analysis, we find that mutation BRAF associated with enhanced selective sensitivity to inhibition when compared either 'wild-type' cells or harbouring a mutation. This dependency was observed mutant regardless tissue lineage, correlated both downregulation cyclin D1 expression the induction G1 arrest. Pharmacological completely abrogated tumour growth xenografts, whereas tumours were only partially inhibited. These data suggest exquisite on activity offer rational therapeutic strategy for this genetically defined subtype.