Pharmacogenomic discovery approaches: will the real genes please stand up?
Genetic inheritance plays a significant role in the interindividual variability of drug response. The field of pharmacogenomics seeks to identify genetic factors that influence drug response, including both those that are inherited and those that arise within tumors, and use this information to improve drug therapy. Candidate gene approaches have led to clinical tests for toxicity avoidance (eg, TPMT, UGT1A1) and efficacy prediction (eg, epidermal growth factor receptor-activating mutations). However, the "right" genes are not known for most anticancer drugs. Strategies for uncovering pharmacogenomic associations vary widely from monogenic candidate gene approaches to polygenic genome-wide approaches. This review will place in context clinically relevant pharmacogenomic discovery approaches, including the relative strengths and weaknesses and the challenges inherent with achieving the goal of individualized therapy.
Walgren
Richard A
RA
Department of Medicine, Washington University School of Medicine, 660 S Euclid Ave, Campus Box 8069, St Louis, MO 63110, USA.
Meucci
Melissa A
MA
McLeod
Howard L
HL
D015894:Genome, Human; D006801:Humans; D010597:Pharmacogenetics / Q000379:methods* / Q000639:trends; D020641:Polymorphism, Single Nucleotide / Q000235:genetics