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Myers JN, Holsinger FC, Bekele BN, et al. Targeted Molecular Therapy for Oral Cancer With Epidermal Growth Factor Receptor Blockade: A Preliminary Report. Arch Otolaryngol Head Neck Surg. 2002;128(8):875–879. doi:10.1001/archotol.128.8.875
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.
Basic science, laboratory investigation.
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 µg/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 0.18µM (R = 0.98) for Tu159 cells and 0.23µM (R = 0.97) for MDA1986 cells. Nude mice were inoculated subcutaneously with 1 × 106 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.
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.
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