Abstract
The expression of epidermal growth factor receptor (EGFR) is a distinctive marker in the biologic progression of prostatic carcinoma (PCa). Gefitinib (‘Iressa’) is an orally active EGFR tyrosine kinase inhibitor, and in clinical trials has shown important antitumor activity in tumors expressing EGFR. Our aim was to demonstrate that Gefitinib was also effective in inhibiting the cellular capabilities leading to metastasis formation.
Methods
The inhibitory effect of Gefitinib on the invasive phenotype of PCa cells was tested in vivo by injecting PC3 cells subcutaneously (Xenograft) or into the left ventricle of nude mice and by daily administration of various doses of Gefitinib.
Results
The tumoral growth of xenograft was significantly inhibited by 150mg/kg Gefitinib with a reduction of 40% in tumor weight. Moreover mice receiving tumoral cells intracardially showed a significant reduction in bone metastases when treated with Gefitinib.
Conclusions
Our data demonstrate that EGF is able to sustain not only cellular growth, but also metastatic progression. For this reason the use of Gefitinib as a therapeutic agent may also be indicated in the control of tumor spreading in EGF responsive tumor cells.
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