O'Donnell Peter H, Dolan M Eileen
Section of Hematology/Oncology and Committee on Clinical Pharmacology and Pharmacogenomics, Department of Medicine, The University of Chicago, Chicago,IL 60637, USA.
Clin Cancer Res. 2009 Aug 1;15(15):4806-14. doi: 10.1158/1078-0432.CCR-09-0344. Epub 2009 Jul 21.
A long-term goal of pharmacogenomics research is the design of individualized therapy based on the genomic sequence of the patient, in order to maximize response and minimize adverse drug reactions. Pharmacoethnicity, or ethnic diversity in drug response or toxicity, is becoming increasingly recognized as an important factor accounting for interindividual variation in anticancer drug responsiveness. Although pharmacoethnicity is determined by genetic and nongenetic factors, there is rapidly accumulating clinical evidence about ethnic differences in the frequencies of polymorphisms within many of the important cancer drug-related genes. This article reviews the current clinical evidence for ethnic differences in anticancer drug disposition and sensitivity while highlighting the challenges, and potential solutions, to acquiring such knowledge. The discovery of "ethnic-specific genetic signatures," representing unique sets of drug susceptibility-governing polymorphisms, may be the outcome of such work. Ultimately, such understanding will further the lofty goal of individualization of chemotherapy based on a person's unique genetic make-up to improve the tolerability and effectiveness of chemotherapy for all patients.
药物基因组学研究的一个长期目标是根据患者的基因组序列设计个体化治疗方案，以实现疗效最大化并将药物不良反应降至最低。药物种族差异，即药物反应或毒性方面的种族多样性，正日益被视为导致抗癌药物反应个体差异的一个重要因素。尽管药物种族差异由遗传和非遗传因素决定，但关于许多重要癌症药物相关基因多态性频率的种族差异，临床证据正在迅速积累。本文回顾了目前关于抗癌药物处置和敏感性种族差异的临床证据，同时强调了获取此类知识所面临的挑战以及潜在的解决方案。发现“种族特异性基因特征”，即代表独特的药物敏感性相关多态性集合，可能是这项工作的成果。最终，这种认识将推动基于个人独特基因构成实现化疗个体化这一崇高目标，从而提高所有患者化疗的耐受性和有效性。
