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.
Highlights
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
In the field of anticancer agents, similar doses are often prescribed to different ethnic populations without consideration of potential differences in pharmacokinetics or pharmacodynamics among populations
Using HapMap lymphoblastoid cell lines (LCLs), Huang and colleagues recently reported on the genetic determinants associated with sensitivity to carboplatin, cisplatin, daunorubicin, and etoposide [59,61,62,63]. In two of those examples, LCLs derived from Caucasians were more susceptible to cytotoxicity induced by carboplatin and daunorubicin than LCLs from Africans, and these observed interethnic differences led to the determination of unique, “ethnic-specific” genetic variants (SNPs and their related genes) associated with chemotherapeutic cytotoxicity susceptibility in each population [61,63]
Summary
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. One salient study of breast cancer patients showed that many CYP3A4, CYP3A5, and CYP2B6 variant polymorphisms are more prevalent in African Americans compared with Caucasians [40], leading the authors to hypothesize that certain polymorphisms that prevent the activation of cyclophosphamide could result in ethnic-specific drug exposure differences.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
