Studies on effective molecular targeted therapy for head and neck cancer

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All the 16 head and neck squamous cell carcinoma (HNSCC) established in our institute expressed EGFR protein and mRNA. Silent heterogous mutation on exon 20 of EGFR gene was detected in all the 16 cell lines, however mutation on exon 19 or exon 20 associated with sensitivity to EGFR inhibitor was not observed in these 16 HNSCC lines.The cell lines with mutation on exon 20 was more sensitive to gefitinib, one of EGFR inhibitors, than the cell lines without mutation (wild type).The exprssions of HER2 protein and mRNA were observed in these 16 cell lines hoeever the growth of these cell lines was not inhibited by the treatment of herceptin, monoclonal antibody against HER2, alone. In 6 of 16 cell lines, the combined treatment of gefitinib and herceptin showed a higher growth inhibition than the treatment of gefitinib alone. The anti-tumor mechanism of the combined treatment is thought to be a blockage of heterodimarization between EGFR and HER.2.On the other hand bevacizumab which is a dual inhibitor of EGFR and VEGF, showed a strong anti-tumor effect in a model using nude mice transplanted with a human HNSCC line. Especially, the tumor treated with bevacizumab and paclitaxel completely disappeared. The induction of apoptosis and inhibition of angiogenesis were confirmed in terms of the anti-tumor mechanisms.