title: A review of VEGF/VEGFR-targeted therapeutics for recurrent glioblastoma.
abstract: Glioblastoma, the most common primary malignant brain tumor among adults, is a highly angiogenic and deadly tumor. Angiogenesis in glioblastoma, driven by hypoxia-dependent and independent mechanisms, is primarily mediated by vascular endothelial growth factor (VEGF), and generates blood vessels with distinctive features. The outcome for patients with recurrent glioblastoma is poor because of ineffective therapies. However, recent encouraging rates of radiographic response and progression-free survival, and adequate safety, led the FDA to grant accelerated approval of bevacizumab, a humanized monoclonal antibody against VEGF, for the treatment of recurrent glioblastoma in May 2009. These results have triggered significant interest in additional antiangiogenic agents and therapeutic strategies for patients with both recurrent and newly diagnosed glioblastoma. Given the potent antipermeability effect of VEGF inhibitors, the Radiologic Assessment in Neuro-Oncology (RANO) criteria were recently implemented to better assess response among patients with glioblastoma. Although bevacizumab improves survival and quality of life, eventual tumor progression is the norm. Better understanding of resistance mechanisms to VEGF inhibitors and identification of effective therapy after bevacizumab progression are currently a critical need for patients with glioblastoma.
authors.affiliation: Department of Surgery, The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC 27710, USA. reard003@mc.duke.edu
authors.forename: David A
authors.initials: DA
authors.lastname: Reardon
authors.forename: Scott
authors.initials: S
authors.lastname: Turner
authors.forename: Katherine B
authors.initials: KB
authors.lastname: Peters
authors.forename: Annick
authors.initials: A
authors.lastname: Desjardins
authors.forename: Sridharan
authors.initials: S
authors.lastname: Gururangan
authors.forename: John H
authors.initials: JH
authors.lastname: Sampson
authors.forename: Roger E
authors.initials: RE
authors.lastname: McLendon
authors.forename: James E
authors.initials: JE
authors.lastname: Herndon
authors.forename: Lee W
authors.initials: LW
authors.lastname: Jones
authors.forename: John P
authors.initials: JP
authors.lastname: Kirkpatrick
authors.forename: Allan H
authors.initials: AH
authors.lastname: Friedman
authors.forename: James J
authors.initials: JJ
authors.lastname: Vredenburgh
authors.forename: Darell D
authors.initials: DD
authors.lastname: Bigner
authors.forename: Henry S
authors.initials: HS
authors.lastname: Friedman
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D016543:Central Nervous System Neoplasms / Q000188:drug therapy* / Q000473:pathology; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D005909:Glioblastoma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D058990:Molecular Targeted Therapy; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors*; D012008:Recurrence; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D042461:Vascular Endothelial Growth Factor A; D040262:Receptors, Vascular Endothelial Growth Factor