Different genetic aberrations of BRAF have been reported in various 
malignancies. BRAF is member of the RAS/RAF/MEK/ERK pathway and constitutive 
activity of this pathway can lead to increased cellular growth, invasion, and 
metastasis. The most common activating BRAF mutation in colorectal cancer is the 
V600E mutation, which is present in 5-15% of all tumors, and up to 80% of tumors 
with high microsatellite instability (MSI) harbor this mutation. BRAF mutation 
is associated with proximal location, higher age, female gender, MSI-H, high 
grade, and mucinous histology, and is a marker of poor prognosis in colorectal 
cancer. The role of BRAF mutation as a predictive marker in respect of EGFR 
targeted treatments is controversial. BRAF V600 selective inhibitors have been 
approved for the treatment of V600 mutation positive metastatic melanoma, but 
the response rates in colorectal cancer are poor. This might be due to innate 
resistance mechanisms of colorectal cancers against the treatment solely 
targeting BRAF. To overcome resistance the combination of treatments, 
simultaneous inhibition of BRAF and MEK or PI3K/mTOR, might emerge as a 
successful therapeutic concept.