神经调节蛋白1
化疗
癌症研究
ERBB3型
肺癌
信号转导
表皮生长因子受体
体内
医学
受体
神经调节蛋白
细胞生物学
ErbB公司
生物
癌症
内科学
肿瘤科
生物技术
作者
Ganapati V. Hegde,Cecile C. de la Cruz,Cecilia Chiu,Navneet Alag,Gabriele Schaefer,Lisa Crocker,Sarajane Ross,David M. Goldenberg,Mark Merchant,Janet Tien,Lily Shao,Leslie Roth,Siao-Ping Tsai,Scott Stawicki,Zhaoyu Jin,Shelby K. Wyatt,Richard A.D. Carano,Yanyan Zheng,E. Alejandro Sweet-Cordero,Yan Wu,Erica Jackson
出处
期刊:Science Translational Medicine
[American Association for the Advancement of Science (AAAS)]
日期:2013-02-06
卷期号:5 (171)
被引量:66
标识
DOI:10.1126/scitranslmed.3004438
摘要
Although standard chemotherapies are commonly used to treat most types of solid tumors, such treatment often results in inadequate response to, or relapse after, therapy. This is particularly relevant for lung cancer because most patients are diagnosed with advanced-stage disease and are treated with frontline chemotherapy. By studying the residual tumor cells that remain after chemotherapy in several in vivo non-small cell lung cancer models, we found that these cells have increased levels of human epidermal growth factor receptor (HER) signaling due, in part, to the enrichment of a preexisting NRG1(HI) subpopulation. Neuregulin 1 (NRG1) signaling in these models can be mediated by either the HER3 or HER4 receptor, resulting in the differential activation of downstream effectors. Inhibition of NRG1 signaling inhibits primary tumor growth and enhances the magnitude and duration of the response to chemotherapy. Moreover, we show that inhibition of ligand-mediated Her4 signaling impedes disease relapse in cases where NRG1 inhibition is insufficient. These findings demonstrate that ligand-dependent Her4 signaling plays an important role in disease relapse.
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