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Controlling tumor invasion: bevacizumab and BMP4 for glioblastoma.

Al's Comment:

The Musella Foundation funded this experiment! The concept is excellent - the thinking was if Avastin cuts off the blood supply to the tumor, the tumor cells will try to find a new blood supply by migrating towards areas of higher oxygen content.  This makes the tumor resistant to Avastin. If you combine Avastin with a drug that stops the invasion, you may prevent the resistance and kill the entire tumor.  We funded a prior research project that showed BMP4 has an anti invasion effect so it seemed like a good candidate for this experiment.


Unfortunately, it didn't work out as expected.  The Avastin did not increase the invasiveness of the tumor!  Since there was no increased invasiveness, the BMP4 didn't have much effect.  Since other experiments we funded have shown that Avastin does increase invasiveness in a different mouse model, I think this experiment should be repeated in a few other models and perhaps try a few different anti-invasive drugs.  

Posted on: 09/14/2013

Future Oncol. 2013 Sep;9(9):1389-96. doi: 10.2217/fon.13.96.
Controlling tumor invasion: bevacizumab and BMP4 for glioblastoma.
Rahman M, Azari H, Deleyrolle L, Millette S, Zeng H, Reynolds BA.
Department of Neurosurgery, University of Florida, Gainesville, FL, USA.
Aim: Bevacizumab has been reported to result in increased tumor invasion when used to treat malignant glioma. We hypothesized that BMP4 would prevent diffuse tumor infiltration induced by bevacizumab for malignant glioma in a xenograft model. Methods: Human glioblastoma (GBM) tumor cells were implanted in the striatum of immunocompromised mice. The animals were treated with bevacizumab and BMP4. Tumor growth and invasion were measured. Results: The bevacizumab-treated mice had increased survival compared with control animals (p = 0.02). BMP4 alone did not result in improved survival (p = 1.0). The bevacizumab (p = 0.006) and bevacizumab plus BMP4 (p = 0.006) groups demonstrated significantly decreased total tumor size compared with control. Tumor invasion was significantly decreased in the bevacizumab (p = 0.005), BMP4 (p = 0.04) alone and bevacizumab plus BMP4 (p = 0.002) groups compared with control. No synergistic effect between bevacizumab and BMP4 was observed. Conclusion: Bevacizumab treatment did not result in diffuse infiltration of human GBM in a mouse xenograft model. BMP4 did have an independent favorable effect on GBM that was not synergistic with bevacizumab treatment.


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