Department of Physiology and Pharmacology, Section of Pharmacogenetics, Karolinska Institutet, Stockholm, Sweden.
Clin Pharmacol Ther. 2018 May;103(5):745-748. doi: 10.1002/cpt.976. Epub 2018 Jan 5.
Personalized drug therapy aims to optimize the efficacy of pharmacological treatments by considering genetic, pathophysiological, dietary, and environmental factors as well as comedications and compliance. A multitude of associations between the specific genetic constitution of the patient and drug pharmacokinetics and pharmacodynamics has been identified in the last decades that encompass mainly common single nucleotide variants (SNVs) and gene copy number variations (CNVs) of importance for the function of genes encoding drug-metabolizing enzymes and transporters involved in drug absorption, distribution, metabolism, and excretion (ADME). In addition, genetic variation in factors encoding the major histocompatibility complex have been helpful to predict immune-mediated drug toxicity. This knowledge has been translated into clinical applications through the implementation of pharmacogenomic biomarkers. Over 230 of such markers that can, to a certain extent, predict drug efficacy or the likelihood of adverse drug reactions (ADRs) are recognized by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) and are included in the drug labels of the respective medication. They are of particular value in cancer therapy to provide information of use to avoid ADRs and lack of response.
个体化药物治疗旨在通过考虑遗传、病理生理、饮食和环境因素以及合并用药和依从性来优化药物治疗的疗效。在过去几十年中，已经确定了患者特定的遗传构成与药物药代动力学和药效学之间的大量关联，这些关联主要包括对编码参与药物吸收、分布、代谢和排泄（ADME）的药物代谢酶和转运体的基因的功能重要的常见单核苷酸变异（SNV）和基因拷贝数变异（CNV）。此外，编码主要组织相容性复合体的因素中的遗传变异有助于预测免疫介导的药物毒性。通过实施药物基因组生物标志物，这些知识已转化为临床应用。美国食品和药物管理局（FDA）和欧洲药品管理局（EMA）已识别出超过 230 种此类生物标志物，这些生物标志物在一定程度上可以预测药物疗效或不良反应（ADR）的可能性，并包含在各自药物的药物标签中。它们在癌症治疗中特别有价值，可以提供有用的信息来避免 ADR 和无反应。
