title: Lung adenocarcinoma with BRAF G469L mutation refractory to vemurafenib.
abstract: BRAF V600E is an emerging drug target in lung cancer, but the clinical significance of non-V600 BRAF mutations in lung cancer and other malignancies is less clear. Here, we report the case of a patient with metastatic lung adenocarcinoma with BRAF G469L mutation refractory to vemurafenib. We calculated a structure model of this very rare type of mutated BRAF kinase to explain the molecular mechanism of drug resistance. This information may help to develop effective targeted therapies for cancers with non-V600 BRAF mutations.
authors.affiliation: Department of Medical Oncology, Luzerner Kantonsspital, Luzern, Switzerland. Electronic address: oliver.gautschi@luks.ch.
authors.forename: Oliver
authors.initials: O
authors.lastname: Gautschi
authors.forename: Solange
authors.initials: S
authors.lastname: Peters
authors.forename: Vincent
authors.initials: V
authors.lastname: Zoete
authors.forename: Franziska
authors.initials: F
authors.lastname: Aebersold-Keller
authors.forename: Klaus
authors.initials: K
authors.lastname: Strobel
authors.forename: Bernhard
authors.initials: B
authors.lastname: Schwizer
authors.forename: Astrid
authors.initials: A
authors.lastname: Hirschmann
authors.forename: Olivier
authors.initials: O
authors.lastname: Michielin
authors.forename: Joachim
authors.initials: J
authors.lastname: Diebold
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics*; D000077192:Adenocarcinoma of Lung; D000368:Aged; D000970:Antineoplastic Agents / Q000737:chemistry / Q000627:therapeutic use*; D003062:Codon; D004252:DNA Mutational Analysis; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D006801:Humans; D007211:Indoles / Q000737:chemistry / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics*; D008297:Male; D008958:Models, Molecular; D008968:Molecular Conformation; D009154:Mutation; D049268:Positron-Emission Tomography; D048493:Proto-Oncogene Proteins B-raf / Q000737:chemistry / Q000235:genetics*; D013449:Sulfonamides / Q000737:chemistry / Q000627:therapeutic use*; D014057:Tomography, X-Ray Computed; D000077484:Vemurafenib
chemical_list: D000970:Antineoplastic Agents; D003062:Codon; D007211:Indoles; D013449:Sulfonamides; D000077484:Vemurafenib; D048493:Proto-Oncogene Proteins B-raf
keywords: BRAF; Biomarker; Dabrafenib; Lung cancer; Melanoma; Targeted therapy; Vemurafenib