Cancer pharmacoethnicity: ethnic differences in susceptibility to the effects of chemotherapy.
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.
O'Donnell
Peter H
PH
Section of Hematology/Oncology and Committee on Clinical Pharmacology and Pharmacogenomics, Department of Medicine, The University of Chicago, Chicago,IL 60637, USA.
Dolan
M Eileen
ME
D018943:Anthracyclines / Q000627:therapeutic use; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use; D004198:Disease Susceptibility / Q000208:ethnology*; D019008:Drug Resistance, Neoplasm / Q000235:genetics* / Q000502:physiology; D005006:Ethnicity / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000208:ethnology*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000208:ethnology* / Q000235:genetics; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D014748:Vinca Alkaloids / Q000627:therapeutic use
D018943:Anthracyclines; D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D018906:Antineoplastic Agents, Alkylating; D014748:Vinca Alkaloids