Anti-VEGF therapies for malignant glioma: treatment effects and escape  mechanisms.

Miletic, Hrvoje; NICLOU, Simone P.; Johansson, Mikael; Bjerkvig, Rolf

doi:10.1517/14728220902806444

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Anti-VEGF therapies for malignant glioma: treatment effects and escape mechanisms.

Miletic, Hrvoje; NICLOU, Simone P.; Johansson, Mikael et al.

2009 • In Expert Opinion on Therapeutic Targets, 13 (4), p. 455-68

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https://hdl.handle.net/10993/60297

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10.1517/14728220902806444

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19335067

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Keywords :

Angiogenesis Inhibitors; Angiogenic Proteins; Antineoplastic Agents; Neoplasm Proteins; VEGFA protein, human; Vascular Endothelial Growth Factor A; EC 2.7.10.1 (Receptors, Vascular Endothelial Growth Factor); Aged; Angiogenesis Inhibitors/pharmacology/therapeutic use; Angiogenic Proteins/metabolism; Animals; Antineoplastic Agents/pharmacology/therapeutic use; Brain Neoplasms/blood supply/drug therapy/metabolism; Clinical Trials as Topic; Disease Progression; Drug Resistance, Neoplasm; Endothelium, Vascular/physiopathology; Glioblastoma/blood supply/drug therapy/metabolism; Glioma/blood supply/drug therapy/metabolism; Humans; Middle Aged; Neoplasm Invasiveness; Neoplasm Proteins/antagonists & inhibitors; Neovascularization, Pathologic/drug therapy; Receptors, Vascular Endothelial Growth Factor/drug effects/physiology; Vascular Endothelial Growth Factor A/antagonists & inhibitors/metabolism; Xenograft Model Antitumor Assays

Abstract :

[en] BACKGROUND: Glioblastoma multiforme (GBM) has a very poor prognosis and novel treatment strategies are urgently needed. GBM appears to be an optimal target for anti-angiogenic therapy as the tumour shows a high degree of endothelial cell proliferation and pro-angiogenic growth factor expression. OBJECTIVE: To examine the role of angiogenic factors (particularly VEGF) in glioma and whether inhibition of these factors can be used as a treatment. METHODS: A review of relevant literature. RESULTS/CONCLUSIONS: Anti-angiogenic therapy has fulfilled the proof of concept in glioma animal models. In glioma patients, the efficacy of anti-angiogenic mono-therapies initially has been disappointing. However recent clinical trials combining bevacizumab, an anti-VEGF antibody, with chemotherapy reported very encouraging response rates. Although randomized phase III clinical trials with anti-angiogenic molecules are not yet available for GBM patients, this treatment regimen is already applied off protocol in several clinical centers. It should be kept in mind though that tumours can develop escape mechanisms. In particular invasive cells, which migrate away from the highly vascularized tumour core, are not targeted by anti-angiogenic therapies. In our opinion, the future of anti-angiogenic therapy will rely on a combination strategy including chemotherapy and drugs that target invasive glioma cells.

Disciplines :

Oncology

Author, co-author :

Miletic, Hrvoje; Department of Biomedicine, University of Bergen, NorLux Neuro-Oncology, Bergen, Norway. Hrvoje.Miletic@biomed.uib.no

NICLOU, Simone P. ; NorLux Neuro-Oncology Laboratory, CRP-Santé, Luxembourg

Johansson, Mikael

Bjerkvig, Rolf

External co-authors :

yes

Language :

English

Title :

Anti-VEGF therapies for malignant glioma: treatment effects and escape mechanisms.

Publication date :

April 2009

Journal title :

Expert Opinion on Therapeutic Targets

ISSN :

1472-8222

eISSN :

1744-7631

Publisher :

Taylor & Francis, United Kingdom

Volume :

Issue :

Pages :

455-68

Peer reviewed :

Peer Reviewed verified by ORBi

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