Cancer pharmacoethnicity: ethnic differences in susceptibility to the effects of chemotherapy

Abstract

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.

Fig. 1

Pharmacoethnicity, or ethnic diversity in drug response or toxicity, results from the combined interaction of many factors, principally differences in environment, local practice habit and regulatory control differences, drug–drug interaction differences, and genetic differences. Pharmacoethnicity impacts global drug development and anticancer drug efficacy because the safe, tolerable, or therapeutic doses may differ among populations on the basis of ethnic factors. The importance of studying pharmacogenetics and pharmacogenomics as factors in pharmacoethnicity is becoming increasingly apparent. See also refs. (1, 2). World map courtesy of http://english.freemap.jp/ and used with permission under the Creative Commons Attribution 3.0 License.