卡巴齐塔塞尔
多西紫杉醇
紫杉烷
前列腺癌
恩扎鲁胺
药理学
医学
癌症研究
癌症
雄激素受体
内科学
雄激素剥夺疗法
乳腺癌
作者
Alan P. Lombard,Chengfei Liu,Cameron M. Armstrong,Vito Cucchiara,Xinwei Gu,Wei Lou,Christopher P. Evans,Allen C. Gao
出处
期刊:Molecular Cancer Therapeutics
[American Association for Cancer Research]
日期:2017-10-01
卷期号:16 (10): 2257-2266
被引量:48
标识
DOI:10.1158/1535-7163.mct-17-0179
摘要
Abstract Advancements in research have added several new therapies for castration-resistant prostate cancer (CRPC), greatly augmenting our ability to treat patients. However, CRPC remains an incurable disease due to the development of therapeutic resistance and the existence of cross-resistance between available therapies. Understanding the interplay between different treatments will lead to improved sequencing and the creation of combinations that overcome resistance and prolong survival. Whether there exists cross-resistance between docetaxel and the next-generation taxane cabazitaxel is poorly understood. In this study, we use C4-2B and DU145 derived docetaxel-resistant cell lines to test response to cabazitaxel. Our results demonstrate that docetaxel resistance confers cross-resistance to cabazitaxel. We show that increased ABCB1 expression is responsible for cross-resistance to cabazitaxel and that inhibition of ABCB1 function through the small-molecule inhibitor elacridar resensitizes taxane-resistant cells to treatment. In addition, the antiandrogens bicalutamide and enzalutamide, previously demonstrated to be able to resensitize taxane-resistant cells to docetaxel through inhibition of ABCB1 ATPase activity, are also able to resensitize resistant cells to cabazitaxel treatment. Finally, we show that resensitization using an antiandrogen is far more effective in combination with cabazitaxel than docetaxel. Collectively, these results address key concerns in the field, including that of cross-resistance between taxanes and highlighting a mechanism of cabazitaxel resistance involving ABCB1. Furthermore, these preclinical studies suggest the potential in using combinations of antiandrogens with cabazitaxel for increased effect in treating advanced CRPC. Mol Cancer Ther; 16(10); 2257–66. ©2017 AACR.
科研通智能强力驱动
Strongly Powered by AbleSci AI