Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
Clinical Pharmacology, Pharmacometrics and DMPK (CPD), MedImmune, South San Francisco, California, USA.
Clin Pharmacol Ther. 2019 Jul;106(1):148-163. doi: 10.1002/cpt.1211. Epub 2018 Oct 6.
Precision medicine aims to use patient genomic, epigenomic, specific drug dose, and other data to define disease patterns that may potentially lead to an improved treatment outcome. Personalized dosing regimens based on tumor drug penetration can play a critical role in this approach. State-of-the-art techniques to measure tumor drug penetration focus on systemic exposure, tissue penetration, cellular or molecular engagement, and expression of pharmacological activity. Using in silico methods, this information can be integrated to bridge the gap between the therapeutic regimen and the pharmacological link with clinical outcome. These methodologies are described, and challenges ahead are discussed. Supported by many examples, this review shows how the combination of these techniques provides enhanced patient-specific information on drug accessibility at the tumor tissue level, target binding, and downstream pharmacology. Our vision of how to apply tumor drug penetration measurements offers a roadmap for the clinical implementation of precision dosing.
精准医学旨在利用患者的基因组、表观基因组、特定药物剂量和其他数据来定义可能导致治疗效果改善的疾病模式。基于肿瘤药物渗透的个性化剂量方案在这种方法中起着至关重要的作用。用于测量肿瘤药物渗透的最先进技术侧重于全身暴露、组织渗透、细胞或分子结合以及药理活性表达。通过计算机模拟方法，可以整合这些信息，弥合治疗方案与与临床结果相关的药理联系之间的差距。本文介绍了这些方法，并讨论了未来的挑战。通过许多实例支持，本综述展示了这些技术的结合如何为肿瘤组织水平的药物可及性、靶标结合和下游药理学提供增强的患者特异性信息。我们对如何应用肿瘤药物渗透测量的设想为精准剂量的临床实施提供了路线图。
