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


CONCLUSIONS
Vandetanib has the potential to be a novel molecular targeted therapy for HNSCC.
Sano
Daisuke
D
Department of Head and Neck Surgery, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.
Fooshee
David R
DR
Zhao
Mei
M
Andrews
Genevieve A
GA
Frederick
Mitchell J
MJ
Galer
Chad
C
Milas
Zvonimir L
ZL
Morrow
Phuong Khanh H
PK
Myers
Jeffrey N
JN
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D004195:Disease Models, Animal; D066246:ErbB Receptors / Q000187:drug effects; D005434:Flow Cytometry; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D058990:Molecular Targeted Therapy; D017239:Paclitaxel / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011799:Quinazolines / Q000494:pharmacology*; D011897:Random Allocation; D012680:Sensitivity and Specificity; D015996:Survival Rate; D014407:Tumor Cells, Cultured / Q000187:drug effects; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
D010880:Piperidines; D011799:Quinazolines; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D040301:Vascular Endothelial Growth Factor Receptor-2; D017239:Paclitaxel; C452423:vandetanib