title: Lapatinib enhances herceptin-mediated antibody-dependent cellular cytotoxicity by up-regulation of cell surface HER2 expression.
abstract: BACKGROUND
  Although it was previously reported that lapatinib combined with Herceptin improved the progression-free survival rate compared with lapatinib alone for patients with Herceptin-refractory HER2-positive metastatic breast cancer, the mechanism is purported to be an antiproliferative effect relating to the synergism of these two agents.
  
  
  METHODS
  We evaluated how lapatinib interacts with Herceptin in HER2-positive breast cancer, with a particular focus on Herceptin-mediated antibody-dependent cellular cytotoxicity (ADCC).
  
  
  RESULTS
  In an in vitro assay, lapatinib induced HER2 expression at the cell surface of HER2-positive breast cancer cell lines, leading to the enhancement of Herceptin-mediated ADCC. Furthermore, we present a case report in which a second Herceptin treatment following lapatinib resulted in the marked shrinkage of multiple metastatic tumors in HER2-positive breast cancer.
  
  
  CONCLUSIONS
  Lapatinib may have the potential to convert Herceptin-refractory to Herceptin-sensitive tumors in HER2-positive breast cancer by up-regulation of the cell surface expression of HER2.
authors.affiliation: First Department of Surgery, University of Yamanashi, Yamanashi, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Maruyama
authors.forename: Kousaku
authors.initials: K
authors.lastname: Mimura
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Izawa
authors.forename: Ayako
authors.initials: A
authors.lastname: Inoue
authors.forename: Shugo
authors.initials: S
authors.lastname: Shiba
authors.forename: Mitsuaki
authors.initials: M
authors.lastname: Watanabe
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Kawaguchi
authors.forename: Masayuki
authors.initials: M
authors.lastname: Inoue
authors.forename: Hisashi
authors.initials: H
authors.lastname: Nogata
authors.forename: Shingo
authors.initials: S
authors.lastname: Inoue
authors.forename: Hideki
authors.initials: H
authors.lastname: Fujii
authors.forename: Koji
authors.initials: K
authors.lastname: Kono
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology*; D015153:Blotting, Western; D004357:Drug Synergism; D005260:Female; D005434:Flow Cytometry; D018734:Genes, erbB-2; D006801:Humans; D000077341:Lapatinib; D008875:Middle Aged; D011799:Quinazolines / Q000494:pharmacology*; D000068878:Trastuzumab; D015854:Up-Regulation
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D011799:Quinazolines; D000077341:Lapatinib; D000068878:Trastuzumab