Committee on Clinical Pharmacology and Pharmacogenomics, University of Chicago, 900 East 57th Street, Chicago, Illinois 60637, USA.
Nat Rev Genet. 2013 Jan;14(1):23-34. doi: 10.1038/nrg3352. Epub 2012 Nov 27.
Genetic variation influences the response of an individual to drug treatments. Understanding this variation has the potential to make therapy safer and more effective by determining selection and dosing of drugs for an individual patient. In the context of cancer, tumours may have specific disease-defining mutations, but a patient's germline genetic variation will also affect drug response (both efficacy and toxicity), and here we focus on how to study this variation. Advances in sequencing technologies, statistical genetics analysis methods and clinical trial designs have shown promise for the discovery of variants associated with drug response. We discuss the application of germline genetics analysis methods to cancer pharmacogenomics with a focus on the special considerations for study design.
遗传变异会影响个体对药物治疗的反应。通过确定对个体患者的药物选择和剂量,了解这种变异有可能使治疗更加安全有效。在癌症的背景下,肿瘤可能具有特定的疾病定义突变,但患者的种系遗传变异也会影响药物反应(包括疗效和毒性),我们在这里重点讨论如何研究这种变异。测序技术、统计遗传学分析方法和临床试验设计的进步为发现与药物反应相关的变异提供了希望。我们讨论了种系遗传学分析方法在癌症药物基因组学中的应用,并重点讨论了研究设计的特殊考虑因素。