Authors' Affiliations: Laboratory for Statistical Analysis, Core for Genomic Medicine; Laboratory for Pharmacogenomics; and Laboratory for Genotyping Development, Core for Genomic Medicine, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
Authors' Affiliations: Laboratory for Statistical Analysis, Core for Genomic Medicine; Laboratory for Pharmacogenomics; and Laboratory for Genotyping Development, Core for Genomic Medicine, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
Clin Cancer Res. 2014 May 15;20(10):2541-52. doi: 10.1158/1078-0432.CCR-13-2755.
In recent years, the utilization of genome-wide association study (GWAS) has proved to be a beneficial method to identify novel common genetic variations not only for disease susceptibility but also for drug efficacy and drug-induced toxicity, creating a field of pharmacogenomics studies. In addition, the findings from GWAS also generate new biologic hypotheses that could improve the understanding of pathophysiology for disease or the mechanism of drug-induced toxicity. This review highlights the implications of GWAS that have been published to date and discusses the successes as well as challenges of using GWAS in cancer pharmacogenomics. The aim of pharmacogenomics is to realize the vision of personalized medicine; it is hoped that through GWAS, novel common genetic variations could be identified to predict clinical outcome and/or toxicity in cancer therapies that subsequently could be implemented to improve the quality of lives of patients with cancer. Nevertheless, given the complexity of cancer therapies, underpowered studies, and large heterogeneity of study designs, collaborative efforts are needed to validate these findings and overcome the limitations of GWA studies before clinical implementation. See all articles in this ccr focus section, "Progress in pharmacodynamic endpoints."
近年来,全基因组关联研究(GWAS)已被证明是一种有益的方法,不仅可以识别疾病易感性的新型常见遗传变异,还可以识别药物疗效和药物诱导毒性的新型常见遗传变异,从而开创了药物基因组学研究领域。此外,GWAS 的发现也产生了新的生物学假设,可以提高对疾病病理生理学或药物诱导毒性机制的理解。这篇综述强调了迄今为止发表的 GWAS 的意义,并讨论了 GWAS 在癌症药物基因组学中的成功和挑战。药物基因组学的目标是实现个性化医疗的愿景;希望通过 GWAS 能够识别新型常见遗传变异,从而预测癌症治疗的临床结果和/或毒性,随后可以实施这些发现以提高癌症患者的生活质量。然而,鉴于癌症治疗的复杂性、研究力度不足以及研究设计的较大异质性,需要开展协作努力来验证这些发现,并克服 GWAS 研究的局限性,然后才能将其应用于临床。在“药效终点的进展”这一 ccr 重点部分中查看所有文章。