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Neuro-Oncology

Angiogenesis as a Therapeutic Target in Malignant Gliomas

^aStephen E. and Catherine Pappas Center for Neuro-Oncology, Department of Neurology, Division of Hematology and Oncology, Massachusetts General Hospital Cancer Center, Boston, Massachusetts, USA; ^bA.A. Martinos Center for Biomedical Imaging, Boston, Massachusetts, USA; ^cDepartment of Radiation Oncology, Massachusetts General Hospital and ^dHarvard Medical School, Boston, Massachusetts, USA

Key Words. Malignant glioma • Glioblastoma • Angiogenesis • Vascular endothelial growth factor • Cerebral edema

Correspondence: Tracy T. Batchelor, M.D., Stephen E. and Catherine Pappas Center for Neuro-Oncology, Massachusetts General Hospital Cancer Center, 55 Fruit Street, Yawkey 9E, Boston, Massachusetts 02114, USA. Telephone: 617-643-1938; Fax: 617-643-2591; e-mail: tbatchelor{at}partners.org

Received December 5, 2008; accepted for publication May 7, 2009; first published online in THE ONCOLOGIST Express on June 1, 2009.

Disclosures: Andrew S. Chi: None; A. Gregory Sorenson: Consultant/advisory role: ACRIN Image Metrix, Genentech, Epix Pharmaceuticals, Millennium, AstraZeneca, Mitsubishi Pharma; Research funding/contracted research: NIH, Siemens Medical Solutions, GE Healthcare, GlaxoSmithKline, Novartis Pharmaceuticals, Exelixis, Schering Plough, Amgen, AstraZeneca; Rakesh K. Jain: Consultant/advisory role: AstraZeneca, Dyax, Millennium; Honoraria: AstraZeneca, Dyax; Ownership interest: SynDevRx; Tracy T. Batchelor: Consultant/advisory role: Millennium, AstraZeneca, ImClone, Exelixis, Vertex, McCleon; Honoraria: Genentech, Schering-Plough, Enzon.

The article discusses bevacizumab (Genentech) and cediranib (AstraZeneca).

The content of this article has been reviewed by independent peer reviewers to ensure that it is balanced, objective, and free from commercial bias. No financial relationships relevant to the content of this article have been disclosed by the independent peer reviewers.

Currently, adult glioblastoma (GBM) patients have poor outcomes with conventional cytotoxic treatments. Because GBMs are highly angiogenic tumors, inhibitors that target tumor vasculature are considered promising therapeutic agents in these patients. Encouraging efficacy and tolerability in preliminary clinical trials suggest that targeting angiogenesis may be an effective therapeutic strategy in GBM patients. However, the survival benefits observed to date in uncontrolled trials of antiangiogenic agents have been modest, and several obstacles have limited their effectiveness. This article reviews the rationale for antiangiogenic agents in GBM, their potential mechanisms of action, and their clinical development in GBM patients. Although challenges remain with this approach, ongoing studies may improve upon the promising initial benefits already observed in GBM patients.