在MYCN驱动的癌症中,CDK7抑制抑制了超增强剂相关的瘤转录
Edmond Chipumuro1, Eugenio Marco2, Camilla L Christensen3
1Department of Pediatric Hematology/Oncology, Dana-Farber Cancer Institute and Boston Children's Hospital, Boston, MA 02215, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
Cell
|November 24, 2014
概括
准循环素依赖性激酶7 (CDK7) 抑制神经母细胞瘤中MYCN驱动的基因放大. 这种方法抑制了小鼠的瘤生长,提供了潜在的新型癌症疗法,没有全身毒性.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 癌症遗传学 癌症遗传学
背景情况:
- MYC瘤蛋白通过基因转录放大驱动瘤生长.
- 抑制MYC功能一直是癌症治疗的挑战.
- 神经母细胞瘤通常涉及MYCN放大,导致侵袭性疾病.
研究的目的:
- 为了研究抑制MYCN增强神经母细胞瘤中循环素依赖性激酶7 (CDK7) 的治疗潜力.
- 评估CDK7抑制对MYCN驱动的转录和瘤生长的影响.
主要方法:
- 使用一种对神经母细胞瘤细胞中向CDK7的共价抑制剂.
- 分析了MYCN基蛋白的下调和全球转录放大.
- 在高风险神经母细胞瘤的小鼠模型中评估瘤回归和全身毒性.
主要成果:
- CDK7抑制导致MYCN下调和抑制MYCN驱动的转录放大.
- 在没有全身毒性的小鼠模型中观察到显著的瘤回归.
- 治疗通过降低超强增强剂相关基因的调节来选择性地向MYCN过度表达的细胞.
结论:
- CDK7抑制有选择地针对MYCN驱动的全球转录放大.
- 这种方法显示出作为MYC驱动的癌症,包括神经母细胞瘤的新疗法战略的希望.
- 选择性向转录机制为癌症治疗提供了一个新的途径.
更多相关视频
相关概念视频
Inhibition of Cdk Activity
6.3K
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
6.3K
Inhibition of CDK Activity
5.7K
5.7K
Induced Pluripotent Stem Cells
6.4K
Stem cells are undifferentiated cells that divide and produce different cell types. Ordinarily, cells that have differentiated into a specific cell type are terminally differentiated; however, scientists have found a way to reprogram these mature cells so that they dedifferentiate and return to an unspecialized, proliferative state. These cells are pluripotent like embryonic stem cells—able to produce all cell types—and are called induced pluripotent stem cells (iPSCs).
Somatic...
Somatic...
6.4K
Abnormal Proliferation
5.5K
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
5.5K
M-Cdk Drives Transition Into Mitosis
6.8K
Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
6.8K
Mitogens and the Cell Cycle
8.5K
Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
8.5K


