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Pharmacogenetics and pharmacogenomics of anticancer agents

¹Instructor of Medicine, Section of Hematology and Oncology, Department of Medicine, University of Chicago, Chicago, IL
²Committee on Clinical Pharmacology and Pharmacogenomics, Cancer Research Center, University of Chicago, Chicago, IL
³Leon O. Jacobson Professor of Medicine, Section of Hematology and Oncology, Department of Medicine, University of Chicago, Chicago, IL

Corresponding author: Section of Hematology and Oncology, Department of Medicine, University of Chicago, 5841 S. Maryland Avenue, MC2115, Chicago, IL, 60637; e-mail: mratain{at}medicine.bsd.uchicago.edu

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DISCLOSURES: Dr. Huang was supported by GM 007019. Dr. Ratain has received royalties related to UGT1A1 genotyping, is a coinventor of pending related patents, and has stock ownership in Applera and Illumina. No other conflict of interest relevant to this article was reported.

Large interindividual variation is observed in both the response and toxicity associated with anticancer therapy. The etiology of this variation is multifactorial, but is due in part to host genetic variations. Pharmacogenetic and pharmacogenomic studies have successfully identified genetic variants that contribute to this variation in susceptibility to chemotherapy. This review provides an overview of the progress made in the field of pharmacogenetics and pharmacogenomics using a five-stage architecture, which includes 1) determining the role of genetics in drug response; 2) screening and identifying genetic markers; 3) validating genetic markers; 4) clinical utility assessment; and 5) pharmacoeconomic impact. Examples are provided to illustrate the identification, validation, utility, and challenges of these pharmacogenetic and pharmacogenomic markers, with the focus on the current application of this knowledge in cancer therapy. With the advance of technology, it becomes feasible to evaluate the human genome in a relatively inexpensive and efficient manner; however, extensive pharmacogenetic research and education are urgently needed to improve the translation of pharmacogenetic concepts from bench to bedside. CA Cancer J Clin 2009;59:42–55. © 2009 American Cancer Society.

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