在复发性/耐药性急性髓性白血病和B细胞恶性瘤中对CDK9抑制剂feruciclib进行一期研究
Matthew S Davids1, Danielle M Brander2, Yesid Alvarado-Valero3
1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.
Blood advances
|December 20, 2024
概括
一种CDK9抑制剂Voruciclib通过减少Mcl-1的作用,在治疗血液性恶性瘤方面表现有前途. 间歇性剂量耐受性良好,支持进一步的试验将其与venetoclax结合用于急性髓性白血病.
科学领域:
- 在瘤学瘤学.
- 药理学 药理学是指药理学的学科.
- 血液学 血液学 血液学
背景情况:
- 骨髓细胞白血病-1 (Mcl-1) 在急性骨髓细胞白血病 (AML) 和B细胞恶性瘤中至关重要,通常会对venetoclax产生抗性.
- 沃鲁西克利布向林依赖性激酶9 (CDK9),间接降低Mcl-1并与venetoclax显示临床前协同作用.
研究的目的:
- 在对复发性或耐药性血液恶性瘤患者的剂量升级研究中评估 voruciclib 的安全性和耐受性.
- 评估在这个患者群体中feruciclib的初步疗效和药学动力学影响.
主要方法:
- 一项对40名患有AML或B细胞恶性瘤的患者进行的evaruciclib剂量升级研究.
- 沃鲁西克利布每天 (1组),然后间歇 (1-14天,2组) 在28天的周期中服用.
- 对不良事件,剂量限制性毒性 (DLT) 和药理动力学标记 (MCL1 mRNA,MYC,NF-κB,p-RNA Pol II) 进行了监测.
主要成果:
- 在第二组中,间歇性varusciclib (200毫克) 剂量在没有DLT的情况下被很好地容忍.
- 常见的不良事件包括腹,恶心,贫血和疲劳.
- 沃鲁西克利布治疗降低了MCL1mRNA,MYC,NF-κB信号传递和RNA聚合酶2酸化.
结论:
- 在患有血液性恶性瘤的患者中,间歇性剂量feruciclib是一种安全和耐受的策略.
- 观察到的药理动力学效应支持进一步调查 voruciclib,特别是与venetoclax结合用于AML治疗.
更多相关视频
![Dynamic Imaging of Chimeric Antigen Receptor T Cells with [18F]Tetrafluoroborate Positron Emission Tomography/Computed Tomography](/_next/image?url=https%3A%2F%2Fcloudfront.jove.com%2FCDNSource%2Fteasers%2F62334.jpg&w=3840&q=50)
相关概念视频
02:34Inhibition of Cdk Activity
4.6K
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...
4.6K
02:15M-Cdk Drives Transition Into Mitosis
5.5K
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...
5.5K