Low-dose angiostatic tyrosine kinase inhibitors improve photodynamic therapy for cancer: lack of vascular normalization
Article first published online: 22 JAN 2014
© 2014 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.
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Journal of Cellular and Molecular Medicine
Volume 18, Issue 3, pages 480–491, March 2014
How to Cite
Weiss, A., van Beijnum, J. R., Bonvin, D., Jichlinski, P., Dyson, P. J., Griffioen, A. W. and Nowak-Sliwinska, P. (2014), Low-dose angiostatic tyrosine kinase inhibitors improve photodynamic therapy for cancer: lack of vascular normalization. Journal of Cellular and Molecular Medicine, 18: 480–491. doi: 10.1111/jcmm.12199
- Issue published online: 27 FEB 2014
- Article first published online: 22 JAN 2014
- Manuscript Accepted: 25 OCT 2013
- Manuscript Received: 24 APR 2013
- Swiss National Science Foundation
- angiogenesis inhibitors;
- axitinib, bevacizumab;
- combination therapy;
- endothelial cells;
- photodynamic therapy;
- tyrosine kinase inhibitors
Photodynamic therapy (PDT) is an effective clinical treatment for a number of different cancers. PDT can induce hypoxia and inflammation, pro-angiogenic side effects, which may counteract its angio-occlusive mechanism. The combination of PDT with anti-angiogenic drugs offers a possibility for improved anti-tumour outcome. We used two tumour models to test the effects of the clinically approved angiostatic tyrosine kinase inhibitors sunitinib, sorafenib and axitinib in combination with PDT, and compared these results with the effects of bevacizumab, the anti-VEGF antibody, for the improvement of PDT. Best results were obtained from the combination of PDT and low-dose axitinib or sorafenib. Molecular analysis by PCR revealed that PDT in combination with axitinib suppressed VEGFR-2 expression in tumour vasculature. Treatment with bevacizumab, although effective as monotherapy, did not improve PDT outcome. In order to test for tumour vessel normalization effects, axitinib was also applied prior to PDT. The absence of improved PDT outcome in these experiments, as well as the lack of increased oxygenation in axitinib-treated tumours, suggests that vascular normalization did not occur. The current data imply that there is a future for certain anti-angiogenic agents to further improve the efficacy of photodynamic anti-cancer therapy.