Targeted Molecular Therapy for Oral Cancer With Epidermal Growth Factor Receptor Blockade: A Preliminary Report | Clinical Pharmacy and Pharmacology | JAMA Otolaryngology–Head & Neck Surgery | JAMA Network
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Original Article
August 2002

Targeted Molecular Therapy for Oral Cancer With Epidermal Growth Factor Receptor Blockade: A Preliminary Report

Author Affiliations

From the Departments of Head and Neck Surgery (Drs Myers, Holsinger, and Li and Mr Jasser), Biostatistics (Dr Bekele), and Cancer Biology (Drs Killion and Fidler), The University of Texas M. D. Anderson Cancer Center, and the Bobby R. Alford Department of Otorhinolaryngology and Communicative Sciences, Baylor College of Medicine (Dr Holsinger), Houston.

Arch Otolaryngol Head Neck Surg. 2002;128(8):875-879. doi:10.1001/archotol.128.8.875

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.

Study Design  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 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.

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.