Lapatinib enhances herceptin-mediated antibody-dependent cellular cytotoxicity by up-regulation of cell surface HER2 expression.
Lapatinib enhances herceptin-mediated antibody-dependent cellular cytotoxicity by up-regulation of cell surface HER2 expression.
复制标题
DOI：
--
复制
发表时间：
2011-09
影响因子：
2
通讯作者：
T. Maruyama;K. Mimura;S. Izawa;A. Inoue;Shugo Shiba;Mitsuaki Watanabe;Y. Kawaguchi;M. Inoue;H. Nogata;S. Inoue;H. Fujii;K. Kono
中科院分区：
文献类型：
--
作者：
T. Maruyama;K. Mimura;S. Izawa;A. Inoue;Shugo Shiba;Mitsuaki Watanabe;Y. Kawaguchi;M. Inoue;H. Nogata;S. Inoue;H. Fujii;K. Kono
背景尽管先前报道拉帕替尼联合赫赛汀与拉帕替尼单药治疗赫赛汀难治性HER2阳性转移性乳腺癌患者相比可改善无进展生存率，但其机制据称是与这两种药物的协同作用有关的抗增殖作用。材料和方法我们评估了拉帕替尼如何与赫赛汀在HER 2阳性乳腺癌中相互作用，特别关注赫赛汀介导的抗体依赖性细胞毒性（ADCC）。结果在体外试验中，拉帕替尼诱导HER2阳性乳腺癌细胞系细胞表面的HER2表达，导致赫赛汀介导的ADCC增强。此外，我们提出了一个病例报告，其中拉帕替尼后第二赫赛汀治疗导致HER2阳性乳腺癌的多个转移性肿瘤明显缩小。结论拉帕替尼可能通过上调HER2的细胞表面表达，使HER2阳性乳腺癌中的赫赛汀难治性肿瘤转化为赫赛汀敏感性肿瘤。
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.