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Lapatinib enhances herceptin-mediated antibody-dependent cellular cytotoxicity by up-regulation of cell surface HER2
Takanori Maruyama1, Kousaku Mimura, Shinichiro Izawa
1First Department of Surgery, University of Yamanashi, Yamanashi, Japan.
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.
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