Pharmacogenomics: Driving Personalized Medicine.

IF 19.3 1区 医学 Q1 PHARMACOLOGY & PHARMACY Pharmacological Reviews Pub Date : 2023-07-01 Epub Date: 2023-03-16 DOI:10.1124/pharmrev.122.000810
Wolfgang Sadee, Danxin Wang, Katherine Hartmann, Amanda Ewart Toland
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Abstract

Personalized medicine tailors therapies, disease prevention, and health maintenance to the individual, with pharmacogenomics serving as a key tool to improve outcomes and prevent adverse effects. Advances in genomics have transformed pharmacogenetics, traditionally focused on single gene-drug pairs, into pharmacogenomics, encompassing all "-omics" fields (e.g., proteomics, transcriptomics, metabolomics, and metagenomics). This review summarizes basic genomics principles relevant to translation into therapies, assessing pharmacogenomics' central role in converging diverse elements of personalized medicine. We discuss genetic variations in pharmacogenes (drug-metabolizing enzymes, drug transporters, and receptors), their clinical relevance as biomarkers, and the legacy of decades of research in pharmacogenetics. All types of therapies, including proteins, nucleic acids, viruses, cells, genes, and irradiation, can benefit from genomics, expanding the role of pharmacogenomics across medicine. Food and Drug Administration approvals of personalized therapeutics involving biomarkers increase rapidly, demonstrating the growing impact of pharmacogenomics. A beacon for all therapeutic approaches, molecularly targeted cancer therapies highlight trends in drug discovery and clinical applications. To account for human complexity, multicomponent biomarker panels encompassing genetic, personal, and environmental factors can guide diagnosis and therapies, increasingly involving artificial intelligence to cope with extreme data complexities. However, clinical application encounters substantial hurdles, such as unknown validity across ethnic groups, underlying bias in health care, and real-world validation. This review address the underlying science and technologies germane to pharmacogenomics and personalized medicine, integrated with economic, ethical, and regulatory issues, providing insights into the current status and future direction of health care. SIGNIFICANCE STATEMENT: Personalized medicine aims to optimize health care for the individual patients with use of predictive biomarkers to improve outcomes and prevent adverse effects. Pharmacogenomics drives biomarker discovery and guides the development of targeted therapeutics. This review addresses basic principles and current trends in pharmacogenomics, with large-scale data repositories accelerating medical advances. The impact of pharmacogenomics is discussed, along with hurdles impeding broad clinical implementation, in the context of clinical care, ethics, economics, and regulatory affairs.

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药物基因组学:推动个性化医疗。
个性化医疗为个人量身定制治疗、疾病预防和健康维护方案,而药物基因组学则是改善疗效和预防不良反应的重要工具。基因组学的进步将传统上侧重于单基因-药物配对的药物遗传学转变为药物基因组学,涵盖了所有"-组学 "领域(如蛋白质组学、转录物组学、代谢组学和元基因组学)。本综述总结了与转化为疗法相关的基因组学基本原理,评估了药物基因组学在融合个性化医疗的各种要素方面所起的核心作用。我们将讨论药物基因(药物代谢酶、药物转运体和受体)的遗传变异、它们作为生物标志物的临床意义以及数十年来药物基因学研究的成果。所有类型的疗法,包括蛋白质、核酸、病毒、细胞、基因和辐照,都能从基因组学中获益,从而扩大了药物基因组学在整个医学中的作用。美国食品药品管理局对涉及生物标记的个性化疗法的批准数量迅速增加,这表明药物基因组学的影响越来越大。作为所有治疗方法的灯塔,癌症分子靶向疗法凸显了药物发现和临床应用的趋势。为了考虑人类的复杂性,包含遗传、个人和环境因素的多组分生物标志物可以指导诊断和治疗,越来越多的人工智能参与其中,以应对极端复杂的数据。然而,临床应用遇到了巨大的障碍,如不同种族群体的有效性未知、医疗保健中的潜在偏见以及现实世界的验证。本综述探讨了与药物基因组学和个性化医疗相关的基础科学和技术,并结合了经济、伦理和监管问题,为医疗保健的现状和未来方向提供了见解。意义声明:个性化医疗旨在通过使用预测性生物标志物来改善疗效和预防不良反应,从而优化针对个体患者的医疗保健。药物基因组学推动了生物标志物的发现,并为靶向治疗药物的开发提供了指导。本综述探讨了药物基因组学的基本原理和当前趋势,大规模数据储存库加速了医学进步。文章从临床护理、伦理学、经济学和监管事务等方面讨论了药物基因组学的影响,以及阻碍广泛临床应用的障碍。
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来源期刊
Pharmacological Reviews
Pharmacological Reviews 医学-药学
CiteScore
34.70
自引率
0.50%
发文量
40
期刊介绍: Pharmacological Reviews is a highly popular and well-received journal that has a long and rich history of success. It was first published in 1949 and is currently published bimonthly online by the American Society for Pharmacology and Experimental Therapeutics. The journal is indexed or abstracted by various databases, including Biological Abstracts, BIOSIS Previews Database, Biosciences Information Service, Current Contents/Life Sciences, EMBASE/Excerpta Medica, Index Medicus, Index to Scientific Reviews, Medical Documentation Service, Reference Update, Research Alerts, Science Citation Index, and SciSearch. Pharmacological Reviews offers comprehensive reviews of new pharmacological fields and is able to stay up-to-date with published content. Overall, it is highly regarded by scholars.
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