NEWS
2011 - 09 - 19 Outstanding publication from the Norlux Neuro-Oncology Laboratory
Olivier Keunen, engineer and imaging specialist and his colleagues at the Norlux Neuro-Oncology Laboratory have published in the reknown journal Proceedings of the National Academy of Sciences (PNAS) an article entitled “Anti-VEGF treatment reduces blood supply and increases tumor cell invasion in glioblastoma”. The Norlux Neuro-Oncology team indeed aims to understand the biological mechanisms underlying the escape mechanisms of malignant gliomas in response to anti-angiogenic therapy.
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Based on initial clinical data, the US Food and Drug Administration (FDA) has approved the use of bevacizumab, an antibody against vascular endothelial growth factor (VEGF) for the treatment of recurrent glioblastoma in 2009. In Europe, the use of bevacizumab has not been approved by the European Medicines Agency (EMA). Bevacizumab (commercial name: Avastin), a drug targeting the tumor vasculature, is a promising, yet controversial, drug in human glioblastoma treatment. Using anatomical and physiological magnetic resonance imaging (MRI) applied to a clinically relevant rat model, the researchers show that bevacizumab causes a strong decrease in contrast enhancement while having only a marginal effect on tumor growth. Interestingly, dynamic contrast-enhanced MRI revealed a significant reduction of the vascular supply, as evidenced by a decrease in intratumoral blood flow and volume. At the morphological level, a strong reduction of large- and medium-sized blood vessels was observed. This was accompanied by increased lactate production suggesting increased hypoxia in the tumor, and a strong increase in infiltrating tumor cells. The tumour thus appears to adapt by activating survival pathways, increasingly relying on glycolysis for its energy supply, and ultimately, adopting a more invasive phenotype.
These important findings might explain why in many patients anti-angiogenic drugs do not lead to a lasting anti-tumor response. The work conducted by the Norlux Neuro-Oncology team under the supervision of Dr. Simone Niclou and Prof. Rolf Bjerkvig, underlines the need to combine anti-angiogenic agents in GBMs with drugs targeting specific signaling or metabolic pathways linked to the glycolytic phenotype.
Olivier Keunen, first author of this publication has conducted the in vivo imaging and he is currently preparing a thesis entitled “Early detection of treatment response in malignant glioma using parametric maps and multi-modal imaging expert system”.
Reference:
Olivier Keunen, Mikael Johansson, Anaïs Oudin, Morgane Sanzey, Siti A. Abdul Rahim, Fred Fack, Frits Thorsen, Torfinn Taxt, Michal Bartos, Radovan Jirik, Hrvoje Miletic, Jian Wang, Daniel Stieber, Linda Stuhr, Ingrid Moen, Cecilie Brekke Rygh, Rolf Bjerkvig, and Simone P. Niclou. Anti-VEGF treatment reduces blood supply and increases tumor cell invasion in glioblastoma. Proc Natl Acad Sci U S A. 2011 Mar 1;108(9):3749-54.