In multidrug-resistant CRC, MAPK pathway is often reprogrammed, usually by the overexpression of RTKs, Ras and Raf; or gain-of-function mutations of Ras and Raf, which sustain the activity of MAPK signalling pathway upon treatment with MAPK and RTK inhibitors, 5-FU and oxaliplatin (Wan et al., 2004; Kavuri et al., 2015; Martinelli et al., 2017; Ressa et al., 2018). Here, RAF1 is linked to colorectal carcinoma.