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The epidermal growth factor receptor (EGFR) and a related family member, HER-2, are often overexpressed simultaneously in patients with a variety of malignant tumors, and the combination may cooperatively promote cancer cell growth and survival. Heterodimerization of EGFR and HER-2 has been known to create intense proliferative signals. Lapatinib (GW572016) is a small molecule that is administrated orally and functions as a reversible inhibitor of both EGFR and HER-2 tyrosine kinases. In the present study, we evaluated the antitumor effect of lapatinib on head and neck squamous cell carcinoma (HNSCC) cell lines in vitro and in vivo. In vivo we examined the antitumor effects of combined treatment with lapatinib and either cisplatin or paclitaxel. In vitro lapatinib displayed antiproliferative effects on HNSCC cells. The IC50 of lapatinib ranged between 13.6 and 60.2 microM after 24-h exposure to lapatinib. A correlation was not observed between results of in vitro proliferation assays for lapatinib and the expression of EGFR or HER-2. In vivo lapatinib displayed antitumor activity, and induced apoptosis in nude mice bearing an established xenograft of YCU-H891 cells. Lapatinib did not significantly inhibit angiogenesis. Combination treatment of lapatinib with cisplatin or paclitaxel enhanced antitumor activity mainly by inducing apoptosis. Inhibition of antiangiogenesis was observed only for combination treatment of lapatinib with paclitaxel (compared to vehicle control). These results suggest that: i) lapatinib has antitumor effects in vitro and in vivo; ii) lapatinib may be more effective in combination with cisplatin or paclitaxel; and iii) lapatinib might provide useful clinical benefits to HNSCC patients.

oncology reports

Antitumor effects of lapatinib (GW572016), a dual inhibitor of EGFR and HER-2, in combination with cisplatin or paclitaxel on head and neck squamous cell carcinoma