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Highly Accessed Review

Pharmacogenomics of chemotherapeutic susceptibility and toxicity

Erika L Moen1, Lucy A Godley12, Wei Zhang3 and M Eileen Dolan12*

Author Affiliations

1 Section of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, IL 60637, USA

2 The University of Chicago Comprehensive Cancer Center, Chicago, IL 60637, USA

3 Department of Pediatrics, The University of Illinois at Chicago, Chicago, IL 60607, USA

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Genome Medicine 2012, 4:90  doi:10.1186/gm391

Published: 30 November 2012

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.

Keywords:
Pharmacogenomics; chemotherapeutics; genome-wide association studies; International HapMap Project; clinical translation