title: Antiangiogenic therapy for glioblastoma: the challenge of translating response rate into efficacy.
abstract: Glioblastoma are one of the mostly vascularized tumors and are histologically characterized by abundant endothelial cell proliferation. Vascular endothelial growth factor (VEGF) is responsible for a degree of vascular proliferation and vessel permeability leading to symptomatic cerebral edema. Initial excitement generated from the impressive radiographic response rates has waned due to concerns of limited long-term efficacy and the promotion of a treatment-resistant phenotype. Reasons for the discrepancy between high radiographic response rates and lack of survival benefit have led to a focus on identifying potential mechanisms of resistance to antiangiogenic therapy. However, equally important is the need to focus on identification of basic mechanisms of action of this class of drugs, determining the optimal biologic dose for each agent and identify the effect of antiangiogenic therapy on oxygen and drug delivery to tumor to optimize drug combinations. Finally, alternatives to overall survival (OS) need to be pursued using the application of validated parameters to reliably assess neurologic function and quality of life.
authors.affiliation: From the Department of Neuro-Oncology, University of Texas MD Anderson Cancer Center, Houston, TX; Center for Neuro-Oncology, Dana-Farber Cancer Institute, Boston, MA; Stephen E. and Catherine Pappas Center for Neuro-Oncology, Massachusetts General Hospital Cancer Center, Boston, MA.
authors.forename: John
authors.initials: J
authors.lastname: de Groot
authors.forename: David A
authors.initials: DA
authors.lastname: Reardon
authors.forename: Tracy T
authors.initials: TT
authors.lastname: Batchelor
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000494:pharmacology / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000503:physiopathology; D015687:Cell Hypoxia / Q000187:drug effects; D002986:Clinical Trials as Topic; D018450:Disease Progression; D004336:Drug Antagonism; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D005909:Glioblastoma / Q000098:blood supply / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D008954:Models, Biological; D022423:Myeloid Cells / Q000502:physiology; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000503:physiopathology; D018579:Patient Selection; D011799:Quinazolines / Q000494:pharmacology / Q000627:therapeutic use; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors* / Q000502:physiology; D016879:Salvage Therapy; D059016:Tumor Microenvironment; D042442:Vascular Endothelial Growth Factors / Q000037:antagonists & inhibitors* / Q000502:physiology; D007211:Indoles
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D000068258:Bevacizumab; D009363:Neoplasm Proteins; D011799:Quinazolines; D040262:Receptors, Vascular Endothelial Growth Factor; D042442:Vascular Endothelial Growth Factors; C500926:cediranib; D007211:Indoles