INTRODUCTION: Antiangiogenic approaches are currently the dominating 
experimental therapeutic strategy in glioblastoma. First enthusiasm was provoked 
by promising radiological response rates and an apparent clinical benefit with 
some of these agents. Major limitations include the modest number of durable 
responses, the lack of cytotoxic antitumor activity, of synergy when combined 
with chemotherapy and of an overall survival benefit.
AREAS COVERED: We review the rationale as well as preclinical and clinical 
evidence for the future development of antiangiogenic agents in glioblastoma. 
The most prominent approach targets VEGF and includes agents such as the VEGF 
antibody bevacizumab, the VEGF receptor fusion protein aflibercept or the 
tyrosine kinase inhibitors cediranib and XL-184. Inhibition of angiogenic 
pathways by small molecules, for example, enzastaurin, or anti-integrin-based 
approaches, for example, cilengitide, represent alternative strategies.
EXPERT OPINION: Enzastaurin and cediranib failed in randomized Phase III trials 
in recurrent glioblastoma, aflibercept in Phase II. By contrast, bevacizumab was 
conditionally approved in many countries. Recently completed Phase III trials 
for bevacizumab and cilengitide in the first-line setting will define the future 
role of these agents. This intense clinical trial activity reflects the hope 
that antiangiogenic agents will become part of the limited therapeutic options 
for glioblastoma.