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Submitted on September 15, 2003
Accepted on October 30, 2003
1 Department of Nuclear Medicine, University of Regensburg, Germany; Department of Clinical Pharmacology and Toxicology, Charité-University Medical School, Benjamin Franklin Medical Center, Berlin, Germany; Department of Trauma and Reconstructive Surgery, Charité-University Medical School, Benjamin Franklin Medical Center, Berlin, Germany.
* To whom correspondence should be addressed. E-mail: johann.schoenberger{at}klinik.uni-regensburg.de.
The process of neoangiogenesis is induced by several mediators. Vascular endothelial growth factor (VEGF) plays a key role in tumor angiogenesis including thyroid carcinomas. The principal aim of this study was to test the hypothesis that inhibition of VEGF activity by PTK787/ZK222584 (PTK/ZK), a specific blocker of both VEGF-receptor tyrosine kinases, could inhibit the growth of a poorly differentiated thyroid cancer.
Human follicular thyroid tumor xenografts were implanted sc into nude mice. Eight days following implantation, the animals were randomized into two groups (n = 10 each group). One group received PTK/ZK daily, and the other was treated with sodium chloride (control). Treatment was orally administered using a gastric tube. All animals were killed after four weeks. Tumors, blood and samples of other organs were taken for further examinations.
Treatment with PTK/ZK induced a 41.4% reduction in tumor volumes. Necrosis of the tumors was detectable earlier in PTK/ZK-treated mice compared with controls. Immunohistochemistry revealed a significant decrease in neoangiogenesis in tumors of PTK/ZK-treated animals. Moreover, no compensatory over-expression of VEGF-protein was detectable in the treated group. The compound was well tolerated by the animals without significant side effects on body weight or in general.
These results showed that VEGF-receptor blockade is a rational approach to the therapy of thyroid cancer. The combination of radioiodine or external radiation with VEGF receptor tyrosine kinase inhibitors might be a new option, especially for poorly differentiated thyroid cancers with limited or no response to conventional therapy.
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