If such cancers are dependent upon MAPK signaling, we reasoned that ERK inhibitors (ERKi) either alone or as part of multi-drug regimens could be of clinical benefit in BRAFV600E-CRC, given the pre-clinical activity observed in melanoma and CRC models resistant to BRAF and MEK inhibitors.20–23 A number of ERK inhibitors, including BVD-523, SCH772984, and GDC-0994 (ref. 24) are currently in pre-clinical and early clinical development, but it remains unclear if these agents will show more favorable clinical activity compared to MEK inhibitors. This evidence concerns the gene BRAF and colorectal carcinoma.