title: BRAF Alterations as Therapeutic Targets in Non-Small-Cell Lung Cancer.
abstract: BACKGROUND
  Several subsets of non-small-cell lung cancer (NSCLC) are defined by molecular alterations acting as tumor drivers, some of them being currently therapeutically actionable. The rat sarcoma (RAS)-rapidly accelerated fibrosarcoma (RAF)-mitogen-activated protein/extracellular signal-regulated kinase kinase (MEK)-extracellular signal-regulated kinase (ERK) pathway constitutes an attractive potential target, as v-Raf murine sarcoma viral oncogene homolog B (BRAF) mutations occur in 2-4% of NSCLC adenocarcinoma.
  
  
  METHODS
  Here, we review the latest clinical data on BRAF serine/threonine kinase inhibitors in NSCLC.
  
  
  RESULTS
  Treatment of V600E BRAF-mutated NSCLC with BRAF inhibitor monotherapy demonstrated encouraging antitumor activity. Combination of BRAF and MEK inhibitors using dabrafenib and trametinib is under evaluation. Preliminary data suggest superior efficacy compared with BRAF inhibitor monotherapy.
  
  
  CONCLUSIONS
  Targeting BRAF alterations represents a promising new therapeutic approach for a restricted subset of oncogene-addicted NSCLC. Prospect ive trials refining this strategy are ongoing. A next step will probably aim at combining BRAF inhibitors and immunotherapy or alternatively improve a multilevel mitogen-activated protein kinase (MAPK) pathway blockade by combining with ERK inhibitors.
authors: *Service d'oncologie médicale, Département d'oncologie, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland; and †Department of Medicine, Roswell Park Cancer Institute, Buffalo, New York.
authors: Tu
authors: T
authors: Nguyen-Ngoc
authors: Hasna
authors: H
authors: Bouchaab
authors: Alex A
authors: AA
authors: Adjei
authors: Solange
authors: S
authors: Peters
mesh_terms: D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D058990:Molecular Targeted Therapy; D009154:Mutation; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf