Pharmacogenomics of chemotherapeutic susceptibility and toxicity
journal contributionposted on 2014-03-18, 00:00 authored by Wei Zhang, Erika L. Moen, Lucy A. Godley, M. Eileen Dolan
ABSTRACT: The goal of personalized medicine is to tailor a patient's treatment strategy on the basis of his or her unique genetic make-up. The field of oncology is beginning to incorporate many of the strategies of personalized medicine, especially within the realm of pharmacogenomics, which is the study of how inter-individual genetic variation determines drug response or toxicity. A main objective of pharmacogenomics is to facilitate physician decision-making regarding optimal drug selection, dose and treatment duration on a patient-by-patient basis. Recent advances in genome-wide genotyping and sequencing technologies have supported the discoveries of a number of pharmacogenetic markers that predict response to chemotherapy. However, effectively implementing these pharmacogenetic markers in the clinic remains a major challenge. This review focuses on the contribution of germline genetic variation to chemotherapeutic toxicity and response, and discusses the utility of genome-wide association studies and use of lymphoblastoid cell lines (LCLs) in pharmacogenomic studies. Furthermore, we highlight several recent examples of genetic variants associated with chemotherapeutic toxicity or response in both patient cohorts and LCLs, and discuss the challenges and future directions of pharmacogenomic discovery for cancer treatment.
The authors are funded by NIH R21HG006367 (WZ, LAG, MED), Pharmacogenomics of Anticancer Agents Research (PAAR) group GM061393 (MED), CA136765 (MED) and NIH/NCI Cancer Biology Training grant T32CA09594 (ELM).
Publisher StatementThis is a copy of an article published in the Genome Medicine © 2012 BioMed Central. © 2012 Moen et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.