RT Journal Article
SR Electronic
T1 Lapatinib Enhances Herceptin-mediated Antibody-dependent Cellular Cytotoxicity by Up-regulation of Cell Surface HER2 Expression
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 2999
OP 3005
VO 31
IS 9
A1 TAKANORI MARUYAMA
A1 KOUSAKU MIMURA
A1 SHINICHIRO IZAWA
A1 AYAKO INOUE
A1 SHUGO SHIBA
A1 MITSUAKI WATANABE
A1 YOSHIHIKO KAWAGUCHI
A1 MASAYUKI INOUE
A1 HISASHI NOGATA
A1 SHINGO INOUE
A1 HIDEKI FUJII
A1 KOJI KONO
YR 2011
UL http://ar.iiarjournals.org/content/31/9/2999.abstract
AB 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. Materials and 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. Conclusion: 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.