用循环生物标记物代替基因分型来确定代谢物表型。

IF 11.2 1区 医学 Q1 PHARMACOLOGY & PHARMACY
Roman Tremmel, Ute Hofmann, Mathias Haag, Elke Schaeffeler, Matthias Schwab
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引用次数: 0

摘要

药物基因组学(PGx)可实现个性化治疗,预测药物反应,避免药物不良反应。目前,药物基因组学主要依靠药物代谢酶或转运体等吸收、分布、代谢和排泄(ADME)靶点的遗传信息来预测患者的表型差异。然而,有证据表明,表型与基因型的一致性是有限的。因此,我们讨论了利用外源性异生物体(如药物鸡尾酒)或内源性化合物进行表型预测的不同表型分析策略。特别是以液体活检为重点的微创方法为预先确定代谢和转运能力提供了巨大的潜力。早期研究表明,利用肝脏释放的外泌体进行 ADME 表型分析是可靠的。此外,药效学建模和人工智能也改善了表型预测。然而,还需要进一步的前瞻性研究来证明基于表型策略的个体化治疗的临床效用,而不仅仅是依赖于遗传学。本综述总结了目前的知识和局限性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Circulating Biomarkers Instead of Genotyping to Establish Metabolizer Phenotypes.

Pharmacogenomics (PGx) enables personalized treatment for the prediction of drug response and to avoid adverse drug reactions. Currently, PGx mainly relies on the genetic information of absorption, distribution, metabolism, and excretion (ADME) targets such as drug-metabolizing enzymes or transporters to predict differences in the patient's phenotype. However, there is evidence that the phenotype-genotype concordance is limited. Thus, we discuss different phenotyping strategies using exogenous xenobiotics (e.g., drug cocktails) or endogenous compounds for phenotype prediction. In particular, minimally invasive approaches focusing on liquid biopsies offer great potential to preemptively determine metabolic and transport capacities. Early studies indicate that ADME phenotyping using exosomes released from the liver is reliable. In addition, pharmacometric modeling and artificial intelligence improve phenotype prediction. However, further prospective studies are needed to demonstrate the clinical utility of individualized treatment based on phenotyping strategies, not only relying on genetics. The present review summarizes current knowledge and limitations.

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来源期刊
CiteScore
27.80
自引率
0.00%
发文量
53
期刊介绍: Since 1961, the Annual Review of Pharmacology and Toxicology has been a comprehensive resource covering significant developments in pharmacology and toxicology. The journal encompasses various aspects, including receptors, transporters, enzymes, chemical agents, drug development science, and systems like the immune, nervous, gastrointestinal, cardiovascular, endocrine, and pulmonary systems. Special topics are also featured in this annual review.
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