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

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

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)349-358
Number of pages10
JournalHead and Neck
Volume33
Issue number3
DOIs
StatePublished - Mar 2011

All Science Journal Classification (ASJC) codes

  • Otorhinolaryngology

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