Document Detail

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.
MedLine Citation:
PMID:  20204279     Owner:  NLM     Status:  MEDLINE    
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.
Norio Kondo; Mamoru Tsukuda; Yukari Ishiguro; Machiko Kimura; Kyoko Fujita; Atsuko Sakakibara; Hideaki Takahashi; Gabor Toth; Hideki Matsuda
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Oncology reports     Volume:  23     ISSN:  1791-2431     ISO Abbreviation:  Oncol. Rep.     Publication Date:  2010 Apr 
Date Detail:
Created Date:  2010-03-05     Completed Date:  2010-06-14     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9422756     Medline TA:  Oncol Rep     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  957-63     Citation Subset:  IM    
Department of Biology and Function in Head and Neck, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan.
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MeSH Terms
Antineoplastic Combined Chemotherapy Protocols / pharmacology*
Apoptosis / drug effects
Carcinoma, Squamous Cell / drug therapy*
Cell Line, Tumor
Cell Proliferation / drug effects
Cisplatin / administration & dosage
Head and Neck Neoplasms / drug therapy*
In Situ Nick-End Labeling
Inhibitory Concentration 50
Paclitaxel / administration & dosage
Quinazolines / administration & dosage
Receptor, Epidermal Growth Factor / drug effects
Receptor, erbB-2 / drug effects
Xenograft Model Antitumor Assays
Reg. No./Substance:
0/Quinazolines; 0/lapatinib; 15663-27-1/Cisplatin; 33069-62-4/Paclitaxel; EC protein, human; EC, Epidermal Growth Factor; EC, erbB-2

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