STAT3 activation confers trastuzumab-emtansine (T-DM1) resistance in HER2-positive breast cancer
文献类型：期刊论文
| 作者 | Wang, Lei; Wang, Quanren; Gao, Mingzhao; Fu, Li; Li, Yun; Quan, Haitian ; Lou, Liguang
|
| 刊名 | CANCER SCIENCE
 |
| 出版日期 | 2018-10 |
| 卷号 | 109期号:10页码:3305-3315 |
| 关键词 | drug resistance leukemia inhibitory factor receptor secreted factor STAT3 trastuzumab-emtansine |
| ISSN号 | 1349-7006 |
| DOI | 10.1111/cas.13761 |
| 文献子类 | Article |
| 英文摘要 | Trastuzumab-emtansine (T-DM1) is an antibody-drug conjugate that has been approved for the treatment of human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. Despite the remarkable efficacy of T-DM1 in many patients, resistance to this therapeutic has emerged as a significant clinical problem. In the current study, we used BT-474/KR cells, a T-DM1-resistant cell line established from HER2-positive BT-474 breast cancer cells, as a model to investigate mechanisms of T-DM1 resistance and explore effective therapeutic regimens. We show here for the first time that activation of signal transducer and activator of transcription 3 (STAT3) mediated by leukemia inhibitory factor receptor (LIFR) overexpression confers resistance to T-DM1. Moreover, secreted factors induced by activated STAT3 in resistant cells limit the responsiveness of cells that were originally sensitive to T-DM1. Importantly, STAT3 inhibition sensitizes resistant cells to T-DM1, both in vitro and in vivo, suggesting that the combination T-DM1 with STAT3-targeted therapy is a potential treatment for T-DM1-refractory patients. |
| WOS关键词 | LEUKEMIA INHIBITORY FACTOR ; DRUG CONJUGATE ; P-GLYCOPROTEIN ; GROWTH-FACTOR ; CELLS ; INTERLEUKIN-6 ; COMBINATION ; METASTASIS ; MECHANISM ; GENOMICS |
| 资助项目 | Science and Technology Commission of Shanghai Municipality[14DZ2294100] ; National Natural Science Foundation of China[81502636] |
| WOS研究方向 | Oncology |
| 语种 | 英语 |
| WOS记录号 | WOS:000446319600030 |
| 出版者 | WILEY |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/279561]  |
| 专题 | 药理学第一研究室 |
| 通讯作者 | Lou, Liguang |
| 作者单位 | Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai, Peoples R China |
| 推荐引用方式 GB/T 7714 | Wang, Lei,Wang, Quanren,Gao, Mingzhao,et al. STAT3 activation confers trastuzumab-emtansine (T-DM1) resistance in HER2-positive breast cancer[J]. CANCER SCIENCE,2018,109(10):3305-3315. |
| APA | Wang, Lei.,Wang, Quanren.,Gao, Mingzhao.,Fu, Li.,Li, Yun.,...&Lou, Liguang.(2018).STAT3 activation confers trastuzumab-emtansine (T-DM1) resistance in HER2-positive breast cancer.CANCER SCIENCE,109(10),3305-3315. |
| MLA | Wang, Lei,et al."STAT3 activation confers trastuzumab-emtansine (T-DM1) resistance in HER2-positive breast cancer".CANCER SCIENCE 109.10(2018):3305-3315. |
入库方式： OAI收割
来源：上海药物研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。