向CDK9在癌症中重新激活表观遗传性沉默的基因
Hanghang Zhang1, Somnath Pandey1, Meghan Travers2
1Fels Institute for Cancer Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA.
Cell
|November 21, 2018
概括
在癌症中,循环素依赖性激酶9 (CDK9) 抑制会重新激活缩的瘤抑制基因. 这种表观遗传疗法恢复了基因表达,并显示出广泛的抗癌活性,为癌症治疗提供了新的策略.
科学领域:
- 分子生物学
- 表观遗传学
- 癌症研究
背景情况:
- 已知可促进转录延长的环林依赖激酶9 (CDK9).
- CDK9还在维持异色区域的基因沉默中发挥着关键作用.
研究的目的:
- 研究CDK9在表观遗传基因沉默中的作用.
- 通过向CDK9来发现癌症的新疗法.
主要方法:
- 活细胞药物查和基因确认.
- 选择性CDK9抑制剂的开发和优化 (MC180295).
- 在体外和体内评估抗癌活性和免疫检查点抑制剂敏感性.
主要成果:
- 抑制CDK9会在癌细胞中重新激活表观遗传沉默的基因.
- 恢复瘤抑制基因的表达和诱导细胞分化.
- 开发了一种具有广泛抗癌功效的高度选择性的CDK9抑制剂 (MC180295).
- 抑制CDK9使瘤对α-PD-1免疫疗法产生敏感性.
结论:
- CDK9对于维持基因沉默至关重要,其抑制是一种可行的癌症表观遗传疗法.
- 选择性CDK9抑制显示出单独和与免疫治疗结合的显著抗癌潜力.
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