RAF1 and colorectal carcinoma: Feedback reactivation of EGFR that in turn activates MAPK via CRAF and RAS is a mechanism of resistance to BRAF inhibitors in CRC, and it is through this mechanism that most of these atypical BRAF mutations are still felt to be oncogenic, and as such potentially targetable using pan-RAF or MEK inhibition [54] (Figure 3).