The present invention relates to methods, compositions and kits concerning resistance to treatment with an anti-cancer agent, specifically an inhibitor of MEK. In particular embodiments, the invention concerns mutations in a MEK sequence that confer resistance to a MEK inhibitor. Identification of such mutations in a MEK sequence allows the identification and design of second-generation MEK inhibitors. Methods and kits for detecting the presence of a mutant MEK sequence in a sample are also provided.
