Sansom Institute, School of Pharmacy and Medical Sciences, University of South Australia Adelaide, SA, Australia.
Ther Clin Risk Manag. 2007 Oct;3(5):751-9.
Over recent decades, basic research has yielded a large volume of data on many potentially clinically relevant genetic determinants of drug efficacy and toxicity. Until recently, most examples involved genes encoding drug-metabolizing enzymes, particularly the cytochromes P450. More recently, rapid advances in genomic technologies have enabled broader, genome-wide searches for determinants of drug response. In parallel with these pharmacogenetic studies, a new drug discovery platform, termed pharmacogenomics, has emerged which utilises genetic information to guide the selection of new drugs most likely to survive increasingly demanding safety and efficacy assessments. Together, these advances are widely promoted as the basis of a new era of drug-based therapeutics tailored to the individual. The extent to which individualized or personalized medicine will emerge as a sustainable new therapeutic paradigm is, however, the topic of much debate. It is clear that an increasingly complex series of barriers must be overcome if we are to successfully harness genomic advances in the clinical setting. Potential barriers may include cost-effectiveness of the test, ethical concerns over the use of DNA, and required educational and equipment infrastructure. Although long overdue, many of these potential barriers are now being subjected to closer examination and as a result, a framework for successful clinical uptake of pharmacogenomics is emerging.
近几十年来，基础研究产生了大量关于许多潜在临床相关药物疗效和毒性的遗传决定因素的数据。直到最近，大多数例子都涉及编码药物代谢酶的基因，特别是细胞色素 P450。最近，基因组技术的快速发展使得对药物反应决定因素进行更广泛的全基因组搜索成为可能。与这些药物遗传学研究同时，出现了一种新的药物发现平台，称为药物基因组学，它利用遗传信息来指导选择最有可能通过日益严格的安全性和疗效评估的新药。这些进展被广泛宣传为个体化治疗的新时代的基础，旨在根据个体量身定制药物治疗。然而，个体化或个性化医学是否会成为一种可持续的新治疗模式，这是一个备受争议的话题。如果我们要在临床环境中成功利用基因组学的进步，显然必须克服一系列日益复杂的障碍。潜在的障碍可能包括测试的成本效益、对 DNA 使用的伦理问题以及所需的教育和设备基础设施。尽管这些潜在的障碍早就应该得到关注，但现在它们正在受到更密切的审查，因此，药物基因组学成功临床应用的框架正在出现。
