title: Targeted molecular therapy for oral cancer with epidermal growth factor receptor blockade: a preliminary report.
abstract: BACKGROUND
  Overexpression of epidermal growth factor receptor (EGF-R) is associated with increased malignant potential and correlates with poor clinical outcome in head and neck cancer. Therefore, inhibition of the EGF-R pathway provides an ideal target for molecular therapy. We examined in vitro and in vivo effects of PKI166, an orally administered EGF-R inhibitor, on 2 human squamous cell carcinoma of the oral cavity cell lines, Tu159 and MDA1986.
  
  
  METHODS
  Basic science, laboratory investigation.
  
  
  RESULTS
  For Western blotting, Tu159 and MDA1986 cells were pretreated for 1 hour and then stimulated with EGF. The EGF-R-specific tyrosine kinase autophosphorylation was inhibited completely by PKI166 at all doses tested (1-10 micro g/mL). By means of a tetrazolium-based viable cell assay, PKI166 was shown to arrest the growth of Tu159 and MDA1986 cells. The inhibitory concentration (50%), calculated from regression lines on the linear portion of the growth inhibition graphs, was 0.18 micro M (R = 0.98) for Tu159 cells and 0.23 micro M (R = 0.97) for MDA1986 cells. Nude mice were inoculated subcutaneously with 1 x 10(6) Tu159 tumor cells and observed for 7 days. Next, daily doses of PKI166 (0, 10, or 50 mg/kg) were delivered by orogastric lavage for 28 days and the animals were observed for tumor growth. PKI166 significantly reduced tumor growth in mice treated for 1 month with oral PKI166 in a dose-dependent fashion.
  
  
  CONCLUSIONS
  Targeted molecular therapy with EGF-R blockade arrests the growth of oral cancer in vitro and reduces its proliferation in an experimental xenograft animal model.
authors.affiliation: Department of Head and Neck Surgery, The University of Texas M. D. Anderson Cancer Center, Houston 77030-4009, USA. jmyers@mdanderson.org
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Myers
authors.forename: F Christopher
authors.initials: FC
authors.lastname: Holsinger
authors.forename: B Nebiyou
authors.initials: BN
authors.lastname: Bekele
authors.forename: Emily
authors.initials: E
authors.lastname: Li
authors.forename: Samar A
authors.initials: SA
authors.lastname: Jasser
authors.forename: Jerald J
authors.initials: JJ
authors.lastname: Killion
authors.forename: Isaiah J
authors.initials: IJ
authors.lastname: Fidler
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000235:genetics*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000627:therapeutic use*; D018390:Gene Targeting; D018773:Genes, erbB-1 / Q000235:genetics; D015316:Genetic Therapy; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D009062:Mouth Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: D066246:ErbB Receptors