在癌细胞亚群中的染色体介导的可逆耐药状态
Sreenath V Sharma1, Diana Y Lee, Bihua Li
1Massachusetts General Hospital Cancer Center, 149 13th Street, Charlestown, MA 02129, USA.
Cell
|April 8, 2010
概括
癌细胞通过IGF-1受体信号传递和RBP2的介导,发展出一种暂时的耐药状态,以幸存化疗. 针对这种可逆现象型提供了一个潜在的治疗策略.
科学领域:
- 在瘤学瘤学.
- 细胞生物学 细胞生物学
- 癌症研究 癌症研究
背景情况:
- 癌细胞的异质性影响治疗反应.
- 在人类瘤细胞系中存在一小部分耐药细胞.
- 了解药物耐受性对于有效的癌症治疗至关重要.
研究的目的:
- 研究癌细胞中可逆药物耐受性的机制.
- 确定消除耐药癌细胞亚种群的治疗点.
- 探索表型异质性在癌症生存中的作用.
主要方法:
- 在人类瘤细胞系中对抗癌剂的急性反应的建模.
- 分析IGF-1受体信号传递在药物耐受性中的作用.
- 研究基因组脱甲基酶RBP2/KDM5A在耐药性表型中的参与.
- 评估IGF-1受体抑制剂和染色素修饰剂的影响.
主要成果:
- 一次性地检测到可逆性耐药细胞的一个小子群.
- 这些细胞的药物敏感性降低了100倍以上.
- 药物耐受性通过IGF-1受体信号和RBP2-依赖的改变染色质状态来维持.
- 耐药性表型是动态调节和暂时获得的.
结论:
- 癌细胞种群利用一个动态的生存策略,包括暂时的耐药性.
- 单个细胞可以反向地采用耐药状态来保护整个人群.
- 向IGF-1受体信号或染色质修饰可以选择性地消除耐药细胞.
- 这为克服治疗耐药性的潜在治疗机会提供了机会.
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