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Targeted Molecular Therapy for Oral Cancer With Epidermal Growth Factor Receptor Blockade
A Preliminary Report
Jeffrey N. Myers, MD, PhD;
F. Christopher Holsinger, MD;
B. Nebiyou Bekele, PhD;
Emily Li, DDS;
Samar A. Jasser, BA;
Jerald J. Killion, PhD;
Isaiah J. Fidler, DVM, PhD
Arch Otolaryngol Head Neck Surg. 2002;128:875-879.
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 x
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.
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.
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