根据瘤增强剂概况的治疗向瘤
Stephen C Mack1,2,3,4, Kristian W Pajtler5,6,7, Lukas Chavez5,6,8
1Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA.
Nature
|December 21, 2017
概括
鉴定一种脑瘤的新治疗点至关重要. 这项研究绘制了活跃的染色质地图,以找到必要的基因,揭示了潜在的药物标,可以减少瘤生长并改善小鼠模型的生存.
科学领域:
- 神经瘤学
- 癌症基因组学
- 表观遗传学
背景情况:
- 脑膜瘤是一个具有挑战性的脑瘤, 缺乏有效的分子点,
- 基因组测序已经推进了精确的瘤学,但许多恶性瘤,包括膜瘤,仍然有未知的或不可向的遗传驱动因素.
- 根据位置和遗传变化,膜瘤被分为分子子组,影响患者的结果和治疗反应.
研究的目的:
- 确定关键的超级增强剂相关基因驱动瘤细胞依赖.
- 发现新的分子点和治疗瘤的途径.
- 在已知遗传驱动因素有限的癌症中建立目标和药物发现框架.
主要方法:
- 在两个不同的队列中绘制42个主要表皮瘤的活性色素景观.
- 分析转录增强剂以识别潜在的瘤基因和关键通路.
- 使用患者衍生的神经圈和小鼠模型来测试治疗干预.
主要成果:
- 活性染色体分析显示了关键的超强增强剂相关基因, 对于瘤细胞的存活至关重要.
- 使用小分子抑制剂或短毛针RNA抑制已确定的点,显著降低了瘤细胞的增殖.
- 在临床前的小鼠模型中,有针对性的抑制导致了生存率的提高.
结论:
- 鉴定转录增强剂是一种可行的策略,用于发现膜瘤等挑战性癌症的治疗点.
- 已确定的点和途径为开发新疗法和其他难以治疗的恶性瘤提供了前景.
- 这项研究为未来的瘤药物发现工作提供了基础,特别是对于缺乏明确的遗传驱动因素的瘤.
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