Sadée Wolfgang, Dai Zunyan
Department of Pharmacology, Comprehensive Cancer Center, College of Medicine and Public Health, The Ohio State University, Columbus, OH 43210-1239, USA.
Hum Mol Genet. 2005 Oct 15;14 Spec No. 2:R207-14. doi: 10.1093/hmg/ddi261.
Despite the marked advances in drug therapy, some patients do not respond favorably or suffer severe adverse drug effects. Pharmacogenetic studies have shown that polymorphisms of drug metabolizing enzymes, transporters and receptors contribute to variable drug response. Owing to the complexity of drug actions, a broader genomics approach aims at finding new drug targets and optimizing therapy for the individual patient. However, pharmacogenomics has made only a few inroads into clinical practice to date. This review evaluates obstacles that need to be overcome. These include the complexity of mechanisms underlying drug response, given singly or in combination, uncertainty about the genetic underpinnings of complex diseases, such as cancer, diabetes, cardiovascular and mental disorders and a lack of quantitative understanding of the scope of genetic variations, even for well-studied genes. By resolving these hurdles, pharmacogenomics will yield significant, but incremental, therapeutic advances paving the way towards personalized health care.
尽管药物治疗取得了显著进展,但仍有一些患者反应不佳或遭受严重的药物不良反应。药物遗传学研究表明,药物代谢酶、转运体和受体的多态性会导致药物反应的差异。由于药物作用的复杂性,更广泛的基因组学方法旨在寻找新的药物靶点并为个体患者优化治疗。然而,迄今为止,药物基因组学在临床实践中仅取得了有限的进展。本综述评估了需要克服的障碍。这些障碍包括单独或联合使用时药物反应背后机制的复杂性、复杂疾病(如癌症、糖尿病、心血管疾病和精神障碍)遗传基础的不确定性,以及即使对于研究充分的基因,对遗传变异范围也缺乏定量的认识。通过解决这些障碍,药物基因组学将取得重大但渐进的治疗进展,为个性化医疗铺平道路。