Primetime for antiangiogenic therapy.
OBJECTIVE
To review the current experience with angiogenesis inhibitors in the treatment of gliomas.


RESULTS
Antiangiogenic therapy has recently reached the clinic with the approval of bevacizumab for recurrent glioblastomas. A number of promising antiangiogenic and vasculature-modifying agents are under investigation for newly diagnosed and recurrent malignant gliomas. A recurrence under ongoing or after antiangiogenic therapy is often characterized by a more aggressive and, in particular, invasive phenotype.


CONCLUSIONS
Despite impressively high radiological response rates in patients with recurrent malignant glioma, the duration of response is usually short-lived, and the observed effect to a large extent may be due to normalization of the disrupted blood-brain barrier and less due to a direct antitumor effect. Overall survival remains poor. Induction of invasive phenotypes and escape with proangiogenic alternative pathways are contributing to resistance. Investigation of combination regimes targeting several pathways will determine the possibilities to overcome the resistance to antiangiogenic therapy in malignant gliomas. This article summarizes the results of recent clinical trials in this field, points towards mechanisms of resistance arising under angiogenesis inhibition and discusses the challenges for the future.
Tabatabai
Ghazaleh
G
Department of Neurology, University Hospital Zurich, Zurich, Switzerland. ghazaleh.tabatabai@usz.ch
Stupp
Roger
R
D020533:Angiogenesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy*; D005910:Glioma / Q000188:drug therapy*; D006801:Humans; D015398:Signal Transduction / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D020533:Angiogenesis Inhibitors; D042461:Vascular Endothelial Growth Factor A