McLeod H L, Evans W E
Department of Medicine, Division of Oncology, Washington University Medical School, St. Louis, Missouri 63110-1093, USA.
Annu Rev Pharmacol Toxicol. 2001;41:101-21. doi: 10.1146/annurev.pharmtox.41.1.101.
There is great heterogeneity in the way humans respond to medications, often requiring empirical strategies to find the appropriate drug therapy for each patient (the "art" of medicine). Over the past 50 years, there has been great progress in understanding the molecular basis of drug action and in elucidating genetic determinants of disease pathogenesis and drug response. Pharmacogenomics is the burgeoning field of investigation that aims to further elucidate the inherited nature of interindividual differences in drug disposition and effects, with the ultimate goal of providing a stronger scientific basis for selecting the optimal drug therapy and dosages for each patient. These genetic insights should also lead to mechanism-based approaches to the discovery and development of new medications. This review highlights the current status of work in this field and addresses strategies that hold promise for future advances in pharmacogenomics.
人类对药物的反应存在很大的异质性,常常需要采用经验性策略来为每位患者找到合适的药物治疗方法(即医学的“艺术”)。在过去50年里,在理解药物作用的分子基础以及阐明疾病发病机制和药物反应的遗传决定因素方面取得了巨大进展。药物基因组学是一个新兴的研究领域,旨在进一步阐明个体间药物处置和效应差异的遗传本质,最终目标是为为每位患者选择最佳药物治疗和剂量提供更坚实的科学依据。这些遗传学见解还应促使基于机制的新药物发现和开发方法的出现。本综述重点介绍了该领域的当前工作状况,并探讨了有望推动药物基因组学未来进展的策略。