Lapatinib Enhances Herceptin-mediated Antibody-dependent Cellular Cytotoxicity by Up-regulation of Cell Surface HER2 Expression

被引：0

作者：

Maruyama, Takanori ^{[1
]}

Mimura, Kousaku ^{[1
]}

Izawa, Shinichiro ^{[1
]}

Inoue, Ayako ^{[1
]}

Shiba, Shugo ^{[1
]}

Watanabe, Mitsuaki ^{[1
]}

Kawaguchi, Yoshihiko ^{[1
]}

Inoue, Masayuki ^{[1
]}

Nogata, Hisashi ^{[2
]}

Inoue, Shingo ^{[1
]}

Fujii, Hideki ^{[1
]}

Kono, Koji ^{[1
]}

机构：

[1] Univ Yamanashi, Dept Surg 1, Chuo Ku, Yamanashi 4093898, Japan

[2] Yamanashi Hosp Social Insurance, Yamanashi, Japan

来源：

ANTICANCER RESEARCH | 2011年 / 31卷 / 09期

关键词：

Lapatinib; HER2; ADCC; breast cancer; Herceptin; METASTATIC BREAST-CANCER; TRASTUZUMAB HERCEPTIN; OVARIAN-CANCER; INHIBITOR; CARCINOMA; GW572016; HER-2/NEU; APOPTOSIS; ONCOGENE; RECEPTOR;

D O I：

暂无

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：2999 / 3005

页数：7

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