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In vitro and in vivo evidence that a combination of lapatinib plus S-1 is a promising treatment for pancreatic cancer.

Authors
  • Komoto, Masahiro
  • Nakata, Bunzo
  • Nishii, Takafumi
  • Kawajiri, Hidemi
  • Shinto, Osamu
  • Amano, Ryosuke
  • Yamada, Nobuya
  • Yashiro, Masakazu
  • Hirakawa, Kosei
Type
Published Article
Journal
Cancer science
Publication Date
Feb 01, 2010
Volume
101
Issue
2
Pages
468–473
Identifiers
DOI: 10.1111/j.1349-7006.2009.01405.x
PMID: 19925494
Source
Medline
License
Unknown

Abstract

Lapatinib is a small molecule inhibitor of both HER2 and the epidermal growth factor receptor (EGFR). We investigated the effect of treatment with lapatinib alone or in combination with a fluoropyrimidine derivative S-1 against pancreatic cancer. The HER2/EGFR expression in each of the four pancreatic cancer cell lines MiaPaca-2, PANC-1, Capan-1 and Capan-2 was measured by flow cytometry. The anti-tumor effects of lapatinib (30 mg/kg) and/or S-1 (10 mg/kg) were evaluated using female BALB/c nude mice xenografts generated using these four cell lines. Synergy between lapatinib and S-1 was examined by median effect analysis in vitro. Resected pancreatic cancer tissues from 137 patients were immunohistochemically stained with anti-human HER2 and EGFR antibodies. The administration of lapatinib as a single agent substantially suppressed tumor growth in vivo of all pancreatic cancer cell lines examined. A strong correlation was observed between HER2 expression and the anti-tumor effect of lapatinib in vivo. Lapatinib synergized with S-1 to inhibit the tumor growth of MiaPaca-2 and PANC-1 xenografts. When used as a single agent in vitro, lapatinib barely inhibit the cell growth of any cell line. However, lapatinib synergized with the anti-tumor activity of the S-1 components 5-fluorouracil and 5-chloro-2,4-dihydrogenase against all cell lines. Immunohistochemical staining demonstrated that 70% of the pancreatic cancers overexpressed HER2 and/or EGFR. Both lapatinib monotherapy and combined treatment with S-1 may be promising treatments for patients with pancreatic cancers; the majority these cancers express lapatinib target molecules.

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