This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Zips, D. Articles by Baumann, M. Search for Related Content PubMed PubMed Citation Articles by Zips, D. Articles by Baumann, M.

Enhanced Susceptibility of Irradiated Tumor Vessels to Vascular Endothelial Growth Factor Receptor Tyrosine Kinase Inhibition

Department of ¹ Radiation Oncology and ² Experimental Center, Medical Faculty Carl Gustav Carus, University of Technology, Dresden, Germany; ³ Department of Biostatistics and Applied Mathematics, University of Texas M.D. Anderson Cancer Center, Houston, Texas; and ⁴ Schering AG, Berlin, Germany

Requests for reprints: Michael Baumann, Department of Radiation Oncology, Medical Faculty Carl Gustav Carus, University of Technology, Fetscherstrasse 74, 01307 Dresden, Germany. Phone: 49-351-458-2095; Fax: 49-351-458-5716; E-mail: michael.baumann{at}mailbox.tu-dresden.de.

Previous experiments with PTK787/ZK222584, a specific inhibitor of vascular endothelial growth factor receptor (VEGFR) tyrosine kinases, using irradiated human FaDu squamous cell carcinoma in nude mice, suggested that radiation-damaged tumor vessels are more sensitive to VEGFR inhibition. To test this hypothesis, the tumor transplantation site (i.e., the right hind leg of nude mice) was irradiated 10 days before transplantation of FaDu to induce radiation damage in the host tissue. FaDu tumors vascularized by radiation-damaged blood vessels appeared later, grew at a slower rate, and showed more necrosis and a smaller vessel area per central tumor section than controls. PTK787/ZK222584 at a daily dose of 50 mg/kg body weight had no impact on growth of control tumors. In contrast, tumors vascularized by radiation-damaged vessels responded to PTK787/ZK222584 with longer latency and slower growth rate than controls, and a trend toward further increase in necrosis, indicating that irradiated tumor vessels are more susceptible to VEGFR inhibition than unirradiated vessels. Although not proving causality, expression analysis of VEGF and VEGFR2 shows that enhanced sensitivity of irradiated vessels to a specific inhibitor of VEGFR tyrosine kinases correlates with increased expression of the molecular target.

This article has been cited by other articles:

				K J Williams, B A Telfer, A M Shannon, M Babur, I J Stratford, and S R Wedge Inhibition of vascular endothelial growth factor signalling using cediranib (RECENTINTM; AZD2171) enhances radiation response and causes substantial physiological changes in lung tumour xenografts Br. J. Radiol., October 1, 2008; 81(Special_Issue_1): S21 - S27. [Abstract] [Full Text] [PDF]

				N. A.J.B. Peters, D. J. Richel, J. J.C. Verhoeff, and L. J.A. Stalpers Bowel Perforation After Radiotherapy in a Patient Receiving Sorafenib J. Clin. Oncol., May 10, 2008; 26(14): 2405 - 2406. [Full Text] [PDF]

				C. Timke, H. Zieher, A. Roth, K. Hauser, K. E. Lipson, K. J. Weber, J. Debus, A. Abdollahi, and P. E. Huber Combination of Vascular Endothelial Growth Factor Receptor/Platelet-Derived Growth Factor Receptor Inhibition Markedly Improves Radiation Tumor Therapy Clin. Cancer Res., April 1, 2008; 14(7): 2210 - 2219. [Abstract] [Full Text] [PDF]

				A. J. Beer, A.-L. Grosu, J. Carlsen, A. Kolk, M. Sarbia, I. Stangier, P. Watzlowik, H.-J. Wester, R. Haubner, and M. Schwaiger [18F]Galacto-RGD Positron Emission Tomography for Imaging of {alpha}v{beta}3 Expression on the Neovasculature in Patients with Squamous Cell Carcinoma of the Head and Neck Clin. Cancer Res., November 15, 2007; 13(22): 6610 - 6616. [Abstract] [Full Text] [PDF]

				S. V. Kozin, F. Winkler, I. Garkavtsev, D. J. Hicklin, R. K. Jain, and Y. Boucher Human Tumor Xenografts Recurring after Radiotherapy Are More Sensitive to Anti-Vascular Endothelial Growth Factor Receptor-2 Treatment than Treatment-Naive Tumors Cancer Res., June 1, 2007; 67(11): 5076 - 5082. [Abstract] [Full Text] [PDF]

				K. J. Williams, B. A. Telfer, A. M. Shannon, M. Babur, I. J. Stratford, and S. R. Wedge Combining radiotherapy with AZD2171, a potent inhibitor of vascular endothelial growth factor signaling: pathophysiologic effects and therapeutic benefit Mol. Cancer Ther., February 1, 2007; 6(2): 599 - 606. [Abstract] [Full Text] [PDF]

				M. R. Horsman and D. W. Siemann Pathophysiologic Effects of Vascular-Targeting Agents and the Implications for Combination with Conventional Therapies Cancer Res., December 15, 2006; 66(24): 11520 - 11539. [Abstract] [Full Text] [PDF]

				C. Cao, J. M. Albert, L. Geng, P. S. Ivy, A. Sandler, D. H. Johnson, and B. Lu Vascular Endothelial Growth Factor Tyrosine Kinase Inhibitor AZD2171 and Fractionated Radiotherapy in Mouse Models of Lung Cancer Cancer Res., December 1, 2006; 66(23): 11409 - 11415. [Abstract] [Full Text] [PDF]

				N. Pore, A. K. Gupta, G. J. Cerniglia, Z. Jiang, E. J. Bernhard, S. M. Evans, C. J. Koch, S. M. Hahn, and A. Maity Nelfinavir Down-regulates Hypoxia-Inducible Factor 1{alpha} and VEGF Expression and Increases Tumor Oxygenation: Implications for Radiotherapy. Cancer Res., September 15, 2006; 66(18): 9252 - 9259. [Abstract] [Full Text] [PDF]

				O. Riesterer, M. Honer, W. Jochum, C. Oehler, S. Ametamey, and M. Pruschy Ionizing radiation antagonizes tumor hypoxia induced by antiangiogenic treatment. Clin. Cancer Res., June 1, 2006; 12(11): 3518 - 3524. [Abstract] [Full Text] [PDF]