title: Targeted molecular therapy of head and neck squamous cell carcinoma with the tyrosine kinase inhibitor vandetanib in a mouse model.
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.
  
  
  CONCLUSIONS
  Vandetanib has the potential to be a novel molecular targeted therapy for HNSCC.
authors.affiliation: Department of Head and Neck Surgery, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Sano
authors.forename: David R
authors.initials: DR
authors.lastname: Fooshee
authors.forename: Mei
authors.initials: M
authors.lastname: Zhao
authors.forename: Genevieve A
authors.initials: GA
authors.lastname: Andrews
authors.forename: Mitchell J
authors.initials: MJ
authors.lastname: Frederick
authors.forename: Chad
authors.initials: C
authors.lastname: Galer
authors.forename: Zvonimir L
authors.initials: ZL
authors.lastname: Milas
authors.forename: Phuong Khanh H
authors.initials: PK
authors.lastname: Morrow
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Myers
mesh_terms: 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
chemical_list: D010880:Piperidines; D011799:Quinazolines; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D040301:Vascular Endothelial Growth Factor Receptor-2; D017239:Paclitaxel; C452423:vandetanib