Antiangiogenesis Treatment for Glioblastoma Multiforme: Challenges and Opportunities

Authors:
Eric T. Wong From Brain Tumor Center & Neuro-Oncology Unit, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, and Department of Neuro-Oncology, H. Lee Moffitt Cancer Center & Research Institute, University of South Florida College of Medicine, Tampa, Florida.

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and
Steven Brem From Brain Tumor Center & Neuro-Oncology Unit, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, and Department of Neuro-Oncology, H. Lee Moffitt Cancer Center & Research Institute, University of South Florida College of Medicine, Tampa, Florida.

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Volume/Issue:
Volume 6: Issue 5
Online Publication Date:
May 2008
DOI:
https://doi.org/10.6004/jnccn.2008.0039
Full access

Angiogenesis is a major hallmark of cancer cells, and glioblastomas are among the most angiogenic tumors. The cascade of angiogenesis is probably initiated by hypoxia, leading to the production of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF). Both VEGF and bFGF have paracrine effects on endothelial cells, pericytes, or both, causing the formation of hyperpermeable tumor blood vessels. Advanced MRI techniques, such as dynamic contrast-enhanced, dynamic susceptibility, and arterial spin labeling MRI, have provided semiquantitative measurements of tumor vascular permeability and perfusion. A decrease in vascular permeability and perfusion can be detected after antiangiogenesis drug treatment, either with monoclonal antibody such as bevacizumab that sequesters VEGF, or small-molecule VEGF receptor tyrosine kinase inhibitors. Therefore, antiangiogenesis therapies are being increasingly adopted for treating glioblastomas. However, caution must be exercised because neural stem cells are also sensitive to antiangiogenesis drugs and the combined effect of ionizing radiation. This article summarizes 30 years of laboratory and clinical research on glioblastoma angiogenesis and discusses its underlying biology, clinical trial results, vascular neuroimaging, and the potential side effects of antiangiogenesis treatment.

Correspondence: Eric T. Wong, MD, Brain Tumor Center & Neuro-Oncology Unit, Harvard Medical School, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA 02215. E-mail: ewong@bidmc.harvard.edu
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Print ISSN:
1540-1405
Online ISSN:
1540-1413
Publisher:
National Comprehensive Cancer Network
Cover Journal of the National Comprehensive Cancer Network
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Copyright:
Copyright © 2008 by the National Comprehensive Cancer Network
Page Numbers:
8
Article Category:
Research Article
Received:
17 Dec 2007
Accepted:
19 Feb 2008
Print Publication Date:
01 May 2008
Online Publication Date:
May 2008
Keywords:
Glioblastomas; angiogenesis; vascular neuroimaging; treatment

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