Our results suggest that given the very similar dose response curves and pathway reactivation profiles between the BRAF inhibitors encorafenib and PLX8394, it will be interesting to evaluate PLX8394 as a potential substitute for encorafenib as part of a combinatorial approach with EGFR and MEK inhibition in patients with BRAF mutant CRC. Here, BRAF is linked to colorectal carcinoma.