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

Authors


  • Jeffrey N. Myers has a commercial research grant from Astra Zeneca.

  • Grant support: This work was supported by AstraZeneca, an American Society of Clinical Oncology Young Investigator Award (P.K. Morrow), The University of Texas M. D. Anderson Cancer Center PANTHEON program, The National Institutes of Health Specialized Program of Research Excellence Grant P50CA097007, The National Research Science Award Institutional Research Training Grant T32CA60374, and The National Institutes of Health Cancer Center Support (Core) Grant CA016672.

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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