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Targeted molecular therapy of head and neck squamous cell carcinoma with the tyrosine kinase inhibitor vandetanib in a mouse model

✍ Scribed by Daisuke Sano; David R. Fooshee; Mei Zhao; Genevieve A. Andrews; Mitchell J. Frederick; Chad Galer; Zvonimir L. Milas; Phuong Khanh H. Morrow; Jeffrey N. Myers

Publisher
John Wiley and Sons
Year
2010
Tongue
English
Weight
367 KB
Volume
33
Category
Article
ISSN
1043-3074

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✦ Synopsis

Abstract

Background

We investigated the effects of vandetanib, an inhibitor of vascular endothelial growth factor receptor 2 (VEGFR‐2) and epidermal growth factor receptor (EGFR), alone and in combination with paclitaxel in an orthotopic mouse model of human head and neck squamous cell carcinoma (HNSCC).

Methods

The in vitro effects of vandetanib (ZACTIMA) were assessed in 2 HNSCC cell lines on cell growth, apoptosis, receptor and downstream signaling molecule expression, and phosphorylation levels. We assessed in vivo effects of vandetanib and/or paclitaxel by measuring tumor cell apoptosis, endothelial cell apoptosis, microvessel density, tumor size, and animal survival.

Results

In vitro, vandetanib inhibited the phosphorylation of EGFR and its downstream targets in HNSCC cells and inhibited proliferation and induced apoptosis of HNSCC cells and extended survival and inhibited tumor growth in nude mice orthotopically injected with human HNSCC.

Conclusion

Vandetanib has the potential to be a novel molecular targeted therapy for HNSCC. © 2010 Wiley Periodicals, Inc. Head Neck, 2010

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