title: BRAF inhibitors in BRAF-V600 mutated primary neuroepithelial brain tumors.
abstract: BACKGROUND
  Primary neuroepithelial brain tumors encompass a wide variety of glial and glioneuronal neoplasms. Malignant tumors, tumors located in surgically inaccessible locations (e.g., eloquent brain areas, deep structures, brain stem) and recurrent or progressive tumors pose considerable treatment challenges and are candidates for novel therapeutics based on molecular insights. Small kinase inhibitors of v-RAF murine sarcoma viral oncogene homologue B1 (BRAF) have shown considerable antineoplastic activity in some tumor types harboring activating BRAF-V600 mutations (e.g., melanoma) and promising data are emerging on BRAF inhibitor therapy of mutation-bearing primary brain tumors.
  
  
  METHODS
  This review summarizes the available data on BRAF-V600 point mutations and the antineoplastic activity and toxicity profiles of BRAF inhibitors in neuroepithelial brain tumors including diffuse gliomas (glioblastomas, astrocytomas, oligodendrogliomas), pilocytic astrocytomas, pleomorphic xanthoastrocytomas and gangliogliomas.
  
  
  CONCLUSIONS
  Activating BRAF-V600 mutations are recurrently found in several glial and glioneuronal brain tumors and the available data indicate that BRAF inhibitors are active and well-tolerated in such tumors. Thus, BRAF inhibitors represent a novel and promising therapeutic opportunity that may alter the disease course of molecularly selected CNS neoplasms in a clinically meaningful way. However, so far the evidence is anecdotal and prospective clinical studies should be conducted.
authors.affiliation: a Department of Medicine I , Medical University of Vienna , Vienna , Austria.|b Comprehensive Cancer Center Vienna, CNS Unit , Medical University of Vienna , Vienna , Austria.
authors.forename: Matthias
authors.initials: M
authors.lastname: Preusser
authors.affiliation: c Institute of Neurology , Medical University of Vienna , Vienna , Austria.|d Department of Molecular Pathology and Neuropathology , Medical University of Lodz , Lodz , Poland.
authors.forename: Michal
authors.initials: M
authors.lastname: Bienkowski
authors.affiliation: b Comprehensive Cancer Center Vienna, CNS Unit , Medical University of Vienna , Vienna , Austria.|e Department of Pathology , Medical University of Vienna , Waehringer Guertel 18-20, 1090 Vienna , Austria.
authors.forename: Peter
authors.initials: P
authors.lastname: Birner
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D018303:Ganglioglioma / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D005910:Glioma / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D006801:Humans; D018302:Neoplasms, Neuroepithelial / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D017354:Point Mutation; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors* / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf
keywords: BRAF; brain tumors; glioma; inhibition