title: Therapeutic targeting of VEGF in the treatment of glioblastoma.
abstract: BACKGROUND
  Glioblastoma (GBM) is the most common and aggressive type of primary malignant brain tumor in adults. Despite therapy with maximal safe surgical resection, radiation and temozolomide, prognosis remains poor at 14.6 months. Hence, there is an urgent need for developing novel therapeutic agents. In GBMs, the balance of angiogenic growth factors is skewed toward pro-angiogenesis and VEGF is identified as the key growth factor responsible for neovasculature. Targeting angiogenesis is hypothesized to arrest tumor growth and hence VEGF is an attractive therapeutic target.
  
  
  METHODS
  The purpose of this review is to discuss VEGF pathway inhibitors, their efficacy as monotherapy or in combination with other drugs, the effects on the radiographic response/assessment for GBMs, mechanisms of resistance and associated biomarkers. A short summary of angiogenesis and of the biological characteristics of angiogenesis will also be provided to enhance the understanding of VEGF pathway inhibitors.
  
  
  CONCLUSIONS
  Therapeutic targeting of VEGF has lead to improvements in progression-free survival in GBM patients without any change in the overall survival. VEGF-targeted therapy remains a promising therapeutic opportunity if improvements in biomarkers, imaging techniques and rational combination therapy are used to help advance the clinical efficacy of this approach.
authors.affiliation: Neurological Institute, Cleveland Clinic, The Rose Ella Burkhardt Brain Tumor and Neuro-Oncology Center, Cleveland, OH, USA.
authors.forename: Lizbeth
authors.initials: L
authors.lastname: Robles Irizarry
authors.forename: Dolores
authors.initials: D
authors.lastname: Hambardzumyan
authors.forename: Ichiro
authors.initials: I
authors.lastname: Nakano
authors.forename: Candece L
authors.initials: CL
authors.lastname: Gladson
authors.forename: Manmeet S
authors.initials: MS
authors.lastname: Ahluwalia
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D019008:Drug Resistance, Neoplasm; D005909:Glioblastoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D009389:Neovascularization, Pathologic; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D042461:Vascular Endothelial Growth Factor A