通过CDK 4/6抑制剂的肝毒性:叙述性综述
Wilfrid H F Wong1, Simona Vasiliu1, Thomas McFarlane2,3
1School of Pharmacy, Faculty of Science, University of Waterloo, Kitchener, Canada.
概括
在转移性乳腺癌患者中,ribociclib在CDK4/6抑制剂中显示出肝损伤的风险最高. 帕尔博西克利布显示的风险最低,而阿贝马西克利布显示的风险最低.
科学领域:
- 在瘤学瘤学.
- 药理学 药理学是指药理学的学科.
- 肝病学 肝病学是一种肝病学.
背景情况:
- 循环素依赖性激酶4/6 (CDK4/6) 抑制剂是治疗激素受体阳性 (HR+),人类表皮因子受体2-阴性 (HER2-) 转移性乳腺癌 (MBC) 的组成部分.
- 这些抑制剂,包括palbociclib,ribociclib和abemaciclib,当与HR+/HER2- MBC的内分泌治疗相结合时,是标准的第一线治疗.
- 了解这些药物的肝毒性特征对于患者安全和治疗优化至关重要.
研究的目的:
- 在HR+/HER2-乳腺癌患者中系统地审查和分析palbociclib,ribociclib和abemaciclib诱导的肝毒性发病率.
- 为了比较这三种CDK4/6抑制剂中药物诱导的肝损伤的比较发病率.
- 总结目前关于CDK4/6抑制剂相关肝毒性的发现,并建议未来的研究方向.
主要方法:
- 在2024年1月24日使用PubMed和Embase数据库进行了全面的文献搜索.
- 该审查包括系统性审查,元分析,随机临床试验 (RCT),安全分析和观察性研究.
- 提取并分析了氨酸氨基转移酶 (ALAT) 和酸氨基转移酶 (ASAT) 升高的数据 (所有等级和等级≥3).
主要成果:
- 在ALAT和ASAT水平上,ribociclib对所有等级 (AG) 和等级≥3 (G3+) 升高的风险最高.
- 在RCT和聚合安全性分析中,里博西基利布显示了AG和G3+ALAT/ASAT升高的最高发病率.
- 在各自的分析中,Palbociclib显示了AG ALAT/ASAT升高的最高发病率,但对AG和G3+升高的总体风险最低.
结论:
- 该综述包括25项研究,表明 ribociclib 与评估的CDK4/6抑制剂中药物诱导的肝毒性风险最高.
- 需要进一步的研究来最终确认和精确量化肝毒性发病率的观察到的差异.
- 对肝损伤概况的比较分析对于HR+/HER2-MBC治疗中的知情临床决策至关重要.
相关概念视频
02:34Inhibition of Cdk Activity
4.9K
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...
4.9K
02:15M-Cdk Drives Transition Into Mitosis
5.7K
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...
5.7K
01:16Hepatic Drug Excretion: Influencing Factors
243
The biliary system of the liver, crucial for bile secretion and drug excretion, comprises intrahepatic bile ducts that merge to form the common hepatic duct. This duct, carrying hepatic bile, combines with the cystic duct, draining the gallbladder and forming the common bile duct, which empties into the duodenum. Bile, produced by hepatic cells lining the bile canaliculi, is composed primarily of water, bile salts, pigments, electrolytes, and lesser amounts of cholesterol and fatty acids. Bile...
243