MAP2K1 V211D

We report the emergence of the novel MEK1 gatekeeper mutation in a patient with BRAF colon cancer treated with the allosteric MEK inhibitor binimetinib and the anti-EGFR antibody panitumumab. Moreover, the mutant exhibits reduced sensitivity to all the allosteric MEK inhibitors tested. Thus this mutation serves as a general resistance mutation for current MEK inhibitors; however, it is sensitive to a newly reported ATP-competitive MEK inhibitor, which therefore could be used to overcome drug resistance.