Journal
CANCER LETTERS
Volume 272, Issue 2, Pages 296-306Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2008.07.018
Keywords
Lapatinib; Gastric cancer; Combination drug therapy
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Funding
- National R&D Program for Cancer Control
- Ministry of Health & Welfare, Republic of Korea [0620300-1]
- Second Stage Brain Korea 21 Project
- Korea Health Promotion Institute [0620300] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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HER2 overexpression is observed in 5-25% of gastric cancers. Lapatinib is a dual inhibitor of the epidermal growth factor receptor and HER2 tyrosine kinase. We examined the antitumor effect of lapatinib in gastric cancer cell lines. Lapatinib induced selective and potent growth inhibition in two HER2-amplified gastric cancer cell lines (SNU-216 and NCI-N87). Lapatinib inhibited the phosphorylation of HER2, EGFR and downstream signaling proteins, resulting in G1 arrest in both cell lines with down-regulation of cMyc and induction of p27(kip1). Lapatinib also induced apoptosis in NCI-N87 which has high HER2 amplification ratio. Lapatinib combined with 5-fluorouracil, cisplatin, oxaliplatin or paclitaxel showed an additive or synergistic effect. These results provide a rationale for the future clinical trials of lapatinib combined with cytotoxic drugs in the treatment of HER2-positive gastric cancer. (c) 2008 Elsevier Ireland Ltd. All rights reserved.
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