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. The gene discussed is BRAF; the disease is melanoma.