循环癌细胞是从具有不同程序的血统中产生的
Yaara Oren1,2, Michael Tsabar1,3,4, Michael S Cuoco1
1Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Nature
|August 12, 2021
概括
癌细胞可以通过进入耐药性持续状态来生存药物治疗. 一项新的研究揭示了特定的代谢和基因表达程序使这些持久细胞能够繁殖, 提供新的治疗点来防止癌症复发.
科学领域:
- 癌症生物学
- 遗传学
- 代谢过程
背景情况:
- 越来越多的非遗传机制被认为是癌症治疗失败的关键因素.
- 癌细胞可以进入耐药性持续状态,在持续的药物暴露下,部分细胞保持增殖.
- 暴露在药物中的持久细胞的增殖能力的机制在很大程度上是未知的.
研究的目的:
- 研究癌症持续细胞增殖能力的非遗传机制.
- 识别与循环相关的不同的谱系和转录/代谢程序.
- 探索耐药性虫群体的治疗弱点.
主要方法:
- 开发西瓜病毒条码系统,同时进行克隆追踪和状态监测.
- 克隆起源,增殖和持续细胞的转录状态分析.
- 研究氧化应激和代谢重编程在持续细胞循环中的作用.
主要成果:
- 循环和非循环的持久性来自不同的细胞系,具有独特的转录和代谢特征.
- 抗氧化剂程序的升级和脂肪酸氧化与癌症类型的持续增殖能力有关.
- 与氧化应激或代谢重编程的干扰会影响循环的比例.
- 在以向疗法治疗的人类瘤中观察到持久性细胞程序.
结论:
- 瓜子系统有效地识别了在药物压力下稀有,繁殖的粘性血统.
- 代谢重编程和抗氧化防御对癌症持续细胞增殖至关重要.
- 针对这些发现的弱点可能提供预防癌症复发和疾病进展的策略.
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