抓住引擎:乳腺癌中的新兴细胞循环点
Jesús Fuentes-Antrás1,2, Philippe L Bedard1, David W Cescon1
1Division of Medical Oncology and Hematology, Department of Medicine, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada.
Clinical and translational medicine
|January 24, 2024
概括
新兴的细胞循环点,如CDK2和WEE1,为抗击乳腺癌提供了新的途径,有可能克服对当前疗法的耐药性,并改善患者的治疗结果.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 药理学 药理学是指药理学的学科.
背景情况:
- 乳腺癌涉及细胞循环中断,导致不受控制的增殖和基因组不稳定.
- 准细胞循环调节器是抗癌的关键策略,但早期尝试面临选择性和毒性方面的挑战.
- 最近的进展揭示了对CDK4/6抑制剂的耐药性机制,重新关注新的细胞循环点.
研究的目的:
- 审查乳腺癌治疗中超出CDK4/6的新兴细胞周期标.
- 讨论这些新目标的生物作用和药物开发潜力.
- 在临床试验中突出显示有希望的安全性和有效性的抑制剂.
主要方法:
- 关于新型细胞周期标的临床前和临床研究的文献综述.
- 对乳腺癌细胞循环调节的基础分子机制的分析.
- 对新兴抑制剂的药物开发策略和临床试验数据的评估.
主要成果:
- 一些新的细胞循环标 (例如CDK2,CDK7,WEE1,AURKA) 在临床前模型中显示出潜力.
- 这些标可以克服对CDK4/6抑制剂的耐药性,并使瘤对免疫治疗敏感.
- 许多新型抑制剂表现出良好的安全性概况和有前途的临床活性.
结论:
- 新兴的细胞循环标代表了克服乳腺癌治疗中抗性的有希望的途径.
- 针对特定的细胞周期组件提供了提高疗效和降低毒性的潜力.
- 需要对这些新型抑制剂进行进一步的临床研究.
相关概念视频
Mitogens and the Cell Cycle
6.5K
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...
6.5K
Inhibition of Cdk Activity
4.8K
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...
4.8K
M-Cdk Drives Transition Into Mitosis
5.6K
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...
5.6K
Molecular Factors Affecting Cell Division
3.1K
Several external and internal factors influence the initiation and inhibition of cell division. For instance, the death of nearby cells or the release of human growth hormone (hGH) promotes cell division. In contrast, lack of hGH or crowding of cells can inhibit cell division.
Several proteins function as internal regulators to ensure each cell cycle stage is completed faithfully before proceeding to the next. Regulator molecules may act directly or influence the activity or production of other...
Several proteins function as internal regulators to ensure each cell cycle stage is completed faithfully before proceeding to the next. Regulator molecules may act directly or influence the activity or production of other...
3.1K
Negative Regulator Molecules
35.4K
Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
35.4K
Positive Regulator Molecules
5.5K
Mitotic cell division results in daughter cells that exactly resemble the parent cell. However, errors in the DNA replication or distribution of genetic material may lead to genetic mutations that may be passed down to every new cell formed from the resulting abnormal cell. Propagation of such mutant cells is restricted through checkpoint mechanisms present at different stages of the cell cycle. These checkpoints involve regulator molecules that either promote or demote cell cycle events.
5.5K


