RAF1 and cancer: Common mechanisms of intrinsic or acquired resistance of colorectal cancer to BRAF- or MEK1/2-inhibitors involve re-activation of the MAPK pathway, e.g., through EGFR-mediated activation of RAS and CRAF, or amplification of the BRAF gene [28,29,30,31], although other mechanisms of resistance involving alterations of cancer cell metabolism can also play an important role.