title: Making sense of MEK1 mutations in intrinsic and acquired BRAF inhibitor resistance.
abstract: In this issue of Cancer Discovery, Shi and colleagues add further insight into the role of exon 3 MEK1 mutations in BRAF inhibitor resistance by demonstrating the presence of P124SMEK1 and I111SMEK1 mutations concurrently with V600E/KBRAF mutations at baseline in 16% of melanoma specimens. Although the presence of P124SMEK1 or I111SMEK1 mutations did not predict for resistance, and these alleles were not selected for upon BRAF inhibition, other exon 3 MEK1 mutations, such as C121S, did convey resistance, suggesting a role for defined exon 3 MEK1 mutations in acquired BRAF inhibitor resistance.
authors.affiliation: Department of Molecular Oncology, Moffitt Cancer Center and Research Institute, Tampa, Florida 33612, USA.
authors.forename: Kim H T
authors.initials: KH
authors.lastname: Paraiso
authors.forename: Keiran S M
authors.initials: KS
authors.lastname: Smalley
mesh_terms: D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D006801:Humans; D048369:MAP Kinase Kinase 1 / Q000235:genetics*; D008297:Male; D008545:Melanoma / Q000235:genetics*; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors* / Q000235:genetics*
chemical_list: C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D048369:MAP Kinase Kinase 1; C482125:MAP2K1 protein, human