一种体内获得的雄激素受体增强剂是晚期前列腺癌的非编码驱动因素
David Y Takeda1, Sándor Spisák2, Ji-Heui Seo2
1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; The Eli and Edythe L. Broad Institute, Cambridge, MA 02142, USA.
Cell
|June 19, 2018
概括
研究人员发现了一种新的雄激素受体 (AR) 增强剂, 针对这种增强剂为晚期前列腺癌提供了潜在的新疗法.
科学领域:
- 癌症学
- 遗传学
- 分子生物学
背景情况:
- 雄激素受体 (AR) 活性是晚期前列腺癌治疗耐药性的关键驱动因素.
- 抗病毒局部的基因放大是一种常见的抗药性机制.
研究的目的:
- 识别和功能性描述促进AR活性和治疗耐药性的新调节因素.
- 探索针对前列腺癌治疗的非编码调控元素的潜力.
主要方法:
- 用基因组编辑来破坏新发现的AR增强剂.
- 在不同的雌激素条件下和在酶胺的存在下进行了增殖测试.
- 分析了原发性前列腺瘤和良性样本的表观遗传数据.
主要成果:
- 一个体内获得的AR增强剂,位于AR基因的中心.
- 通过抑制AR水平,这种增强剂的干扰降低了癌细胞的增殖.
- 插入增强剂的额外副本增加了增殖和降低了对胺的敏感性,特别是在低雄激素条件下.
结论:
- 确定的AR增强剂在推动前列腺癌的进展和治疗耐药性方面发挥着关键作用.
- 在初级瘤中表观基因分析对于理解耐药性机制至关重要.
- 基因组编辑是描述非编码元素及其功能影响的宝贵工具.
- 针对AR调节元件在晚期前列腺癌中是一个有前途的治疗漏洞.
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