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HIGUCHI Ryota
Department School of Medicine(Yachiyo Medical Center), School of Medicine Position Assistant Professor |
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| Article types | Original article |
| Language | English |
| Peer review | Peer reviewed |
| Title | Molecular targeting of HER2-overexpressing biliary tract cancer cells with trastuzumab emtansine, an antibody-cytotoxic drug conjugate. |
| Journal | Formal name：Cancer chemotherapy and pharmacology Abbreviation：Cancer Chemother Pharmacol ISSN code：14320843/03445704 |
| Volume, Issue, Page | 83(4),pp.659-671 |
| Author and coauthor | Yamashita-Kashima Yoriko, Yoshimura Yasushi, Fujimura Takaaki, Shu Sei, Yanagisawa Mieko, Yorozu Keigo, Furugaki Koh, Higuchi Ryota, Shoda Junichi, Harada Naoki |
| Publication date | 2019/04 |
| Summary | PURPOSE:Trastuzumab emtansine (T-DM1) provides clinical benefit in breast cancers overexpressing human epidermal growth factor receptor 2 (HER2). However, its efficacy against biliary tract cancers (BTC) has not been evaluated. In this study, the effectiveness of T-DM1 in various BTC cell lines and xenograft models with different levels of HER2 expression was investigated.METHODS:HER2 expression status in xenografts and patient tissue microarrays was assessed by immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH). Cell-surface HER2 expression levels and cell growth inhibition in response to T-DM1 were examined in 17 BTC cell lines. The antitumor activity of T-DM1 was evaluated in four xenograft mouse models with different levels of HER2 expression. The effects of T-DM1 on HER2 signaling, antibody-dependent cell-mediated cytotoxicity (ADCC), cell cycle, and apoptosis were assessed in vitro.RESULTS:Cell-surface expression of HER2 was observed in both gallbladder carcinoma and cholangiocarcinoma tissues. The anti-proliferative activity of T-DM1 was higher in BTC cell lines and breast cancer cell lines with higher levels of HER2 expression. The HER2 status (IHC score|HER2-to-CEP17 ratio by FISH testing) of each BTC xenograft was 3 +|8.3 for KMCH-1, 2 +|4.7 for Mz-ChA-1, 1 +/0|1.4 for OCUG-1, and 0|1.1 for KKU-100, and T-DM1 showed antitumor activity in proportion to the HER2 status. T-DM1 inhibited HER2 signaling and induced ADCC, mitotic arrest, and apoptosis in KMCH-1 cells.CONCLUSIONS:T-DM1 exhibited preclinical activity in HER2-overexpressing BTC. Further evaluation in clinical studies is warranted. |
| DOI | 10.1007/s00280-019-03768-8 |
| PMID | 30659304 |