Journal
DRUG METABOLISM AND PHARMACOKINETICS
Volume 27, Issue 1, Pages 122-131Publisher
JAPANESE SOC STUDY XENOBIOTICS
DOI: 10.2133/dmpk.DMPK-11-RV-084
Keywords
P450 2D6; MRP2; MDR1; UGT; SULT; single nucleotide polymorphism; endoxifen; estrogen receptor
Categories
Ask authors/readers for more resources
Tamoxifen has been widely used for the prevention of recurrence in patients with hormone receptor-positive breast cancer. Tamoxifen requires metabolic activation by cytochrome P450 (CYP) enzymes for formation of active metabolites, 4-hydroxytamoxifen and endoxifen, which have 30- to 100-fold greater affinity to the estrogen receptor and the potency to suppress estrogen-dependent breast cancer cell proliferation. CYP2D6 is a key enzyme in this metabolic activation and it has been suggested that the genetic polymorphisms of CYP2D6 influence the plasma concentrations of active tamoxifen metabolites and clinical outcomes for breast cancer patients treated with tamoxifen. The genetic polymorphisms in the other drug-metabolizing enzymes, including other CYP isoforms, sulfotransferases and UDP-glucuronosyltransferases might contribute to individual differences in the tamoxifen metabolism and clinical outcome of tamoxifen therapy although their contributions would be small. Recently, involvement of a drug transporter in the disposition of active tamoxifen metabolites was identified. The genetic polymorphisms of transporter genes have the potential to improve the prediction of clinical outcome for the treatment of hormone receptor-positive breast cancer. This review summarizes current knowledge on the roles of polymorphisms in the drug-metabolizing enzymes and transporters in tamoxifen pharmacogenomics.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available