Scientific Publications by FDA Staff

Cancer Res 2007 Oct 15;67(20):9609-12

Silent polymorphisms speak: how they affect pharmacogenomics and the treatment of cancer.

Sauna ZE, Kimchi-Sarfaty C, Ambudkar SV, Gottesman MM

Gottesman MM (reprint author), NCI, Cell Biol Lab, Canc Res Ctr, NIH, 37 Convent Dr,Room 2108, Bethesda, MD 20892 USA NCI, Cell Biol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA

Polymorphisms in the human genome contribute to wide variations in how individuals respond to medications, either by changing the pharmacokinetics of drugs or by altering the cellular response to therapeutic agents. The goal of the emerging discipline of pharmacogenomics is to personalize therapy based on an individual's genotype. Due to the relatively large frequency of single-nucleotide polymorphisms (SNP) in the human genome, synonymous SNPs are often disregarded in many pharmacogenomic studies based on the assumption that these are silent. We have shown recently that synonymous SNPs in ABCB1 (P-glycoprotein), which is implicated both in determining drug pharmacokinetics and multidrug resistance in human cancer cells, can affect protein conformation and function. We discuss the importance of polymorphisms in drug metabolizing enzymes and transporters in anticancer therapy and suggest that synonymous polymorphisms may play a more significant role than is currently assumed. [Cancer Res 2007;67(20):9609-12].