Recently, a third class of BRAF mutants was described, corresponding to those that have impaired kinase activity or are kinase-died: these mutants bind more tightly than WT BRAF to RAS-GTP and their binding to WT CRAF is enhanced, leading to increased ERK signaling; in colorectal cancer with class 1 BRAF mutants, RAS is typically activated by receptor tyrosine kinase signaling [123]. This evidence concerns the gene EPHB2 and colorectal cancer.