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为了药物组合治疗的安全性,利用多器官模型

Valentin Mieville¹, Jakub Gubala¹, Seungsu Han²

¹School of Pharmaceutical Sciences, Faculty of Science, University of Geneva, Geneva 1211, Switzerland; Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, Geneva 1211, Switzerland; Translational Research Center in Oncohaematology, Geneva 1211, Switzerland.

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

|December 11, 2025

概括

一个新的体外平台评估多药组合在脏和肝脏等器官中的毒性. 生物相关的模型对于预测严重的药物诱导毒性至关重要,与简单的细胞系不同.

科学领域:

药理学药理学是指药理学的学科.
毒理学毒理学毒理学
生物医学工程生物医学工程

背景情况:

评估多种药物组合的全身毒性对于个性化医学至关重要.
现有的方法可能无法准确预测器官特异性毒性或组合效应.
对于有效的药物开发,需要临床相关的时间框架.

研究的目的:

开发和验证一个简化的体外平台,用于评估多种药物组合的系统毒性.
为了比较不同细胞模型对药物诱导毒性的预测能力.
评估多种药物组合的器官特异性毒性概况.

主要方法:

开发一个多器官体外平台,使用,肝脏和心脏的细胞模型.
使用平台评估两种多药组合 (C2和REMP).
简单细胞系和先进的有机体/球体模型之间的毒性反应的比较.

主要成果:

该平台为多种药物组合确定了不同的器官特异性毒性概况.
一些药物诱导的毒性在组合治疗中加剧.
高级模型 (有机体,球体) 与简单细胞系相比,显示出更高的灵敏度和更好的毒性严重性预测.
与更简单的细胞模型相比,C2组合在器官和分化肝细胞球体中显示出明显更高的毒性.
乳酸脱酶释放表明对C2有显著的毒性.

结论:

生物相关的体外平台对于准确的药物组合系统毒性评估至关重要.
简单的细胞系可能会低估药物诱导毒性的严重性.
开发的平台显示了在个性化癌症治疗开发中早期毒性查的翻译潜力.

关键词:

癌症癌症癌症癌症癌症心脏毒性心脏毒性药物组合是药物组合.药物相互作用药物相互作用肝毒性肝毒性肝毒性在体外 (in vitro) 的情况下.毒性毒性毒性查检查查检查查检查查检查

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