論文 - 詳細
| RRC ID | 64967 |
|---|---|
| 著者 | Nam AR, Kim JW, Cha Y, Ha H, Park JE, Bang JH, Jin MH, Lee KH, Kim TY, Han SW, Im SA, Kim TY, Oh DY, Bang YJ. |
| タイトル | Therapeutic implication of HER2 in advanced biliary tract cancer. |
| ジャーナル | Oncotarget |
| Abstract |
Currently, there is no validated therapeutic target for biliary tract cancer (BTC). This study aimed to investigate the pre-clinical and clinical implication of HER2 as a therapeutic target in BTC. We established two novel HER2-amplified BTC cell lines, SNU-2670 and SNU-2773, from gallbladder cancer patients. SNU-2670 and SNU-2773 cells were sensitive to trastuzumab, dacomitinib, and afatinib compared with nine HER2-negative BTC cell lines. Dacomitinib and afatinib led to G1 cell cycle arrest in SNU-2773 cells and apoptosis in SNU-2670 cells. Furthermore, dacomitinib, afatinib, and trastuzumab showed synergistic cytotoxicity when combined with some cytotoxic drugs including gemcitabine, cisplatin, paclitaxel, and 5-fluorouracil. In a SNU-2670 mouse xenograft model, trastuzumab demonstrated a good anti-tumor effect as a monotherapy and in combination with gemcitabine increasing apoptosis. In our clinical data, 13.0% of patients with advanced BTC were defined as HER2-positive. Of these, three patients completed HER2-targeted chemotherapy. Two of them demonstrated a partial response, and the other one showed stable disease for 18 weeks. In summary, these pre-clinical and clinical data suggest that HER2 could be a therapeutic target, and that a HER2-targeting strategy should be developed further in patients with HER2-positive advanced BTC. |
| 巻・号 | 7(36) |
| ページ | 58007-58021 |
| 公開日 | 2016-9-6 |
| DOI | 10.18632/oncotarget.11157 |
| PII | 11157 |
| PMID | 27517322 |
| PMC | PMC5295408 |
| MeSH | Adenocarcinoma / diagnosis Adenocarcinoma / drug therapy* Adenocarcinoma / genetics Adenocarcinoma / pathology Adult Aged Animals Antineoplastic Agents / pharmacology* Antineoplastic Agents / therapeutic use Antineoplastic Combined Chemotherapy Protocols / pharmacology* Antineoplastic Combined Chemotherapy Protocols / therapeutic use Apoptosis / drug effects Cell Line, Tumor Drug Evaluation, Preclinical Female Fluorodeoxyglucose F18 / administration & dosage Gallbladder / diagnostic imaging Gallbladder / pathology Gallbladder Neoplasms / diagnostic imaging Gallbladder Neoplasms / drug therapy* Gallbladder Neoplasms / genetics Gallbladder Neoplasms / pathology Gene Amplification Humans Immunohistochemistry Lymphatic Metastasis Male Mice Mice, Inbred BALB C Mice, Nude Middle Aged Molecular Targeted Therapy / methods Positron-Emission Tomography Receptor, ErbB-2 / antagonists & inhibitors* Receptor, ErbB-2 / genetics Receptor, ErbB-2 / metabolism Signal Transduction / drug effects Treatment Outcome Xenograft Model Antitumor Assays |
| IF | 5.168 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 5 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | HuCCT1(RCB1960) TFK-1(RCB2537) |