Potential role of UGT pharmacogenetics in cancer treatment and prevention: focus on tamoxifen.
Tamoxifen (TAM) is a selective estrogen receptor modulator that is widely used in the prevention and treatment of estrogen receptor-positive (ER(+)) breast cancer. Its use has significantly contributed to a decline in breast cancer mortality, since breast cancer patients treated with TAM for 5 years exhibit a 30-50% reduction in both the rate of disease recurrence after 10 years of patient follow-up and occurrence of contralateral breast cancer. However, in patients treated with TAM there is substantial interindividual variability in the development of resistance to TAM therapy, and in the incidence of TAM-induced adverse events, including deep vein thrombosis, hot flashes, and the development of endometrial cancer. This article will focus on the UDP glucuronosyltransferases, a family of metabolizing enzymes that are responsible for the deactivation and clearance of TAM and TAM metabolites, and how interindividual differences in these enzymes may play a role in patient response to TAM.
Lazarus
Philip
P
Cancer Control and Population Sciences Program, Penn State Cancer Institute, Department of Pharmacology, Penn State University College of Medicine, Hershey, Pennsylvania 17033, USA. plazarus@psu.edu
Blevins-Primeau
Andrea S
AS
Zheng
Yan
Y
Sun
Dongxiao
D
D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000517:prevention & control*; D045744:Cell Line, Tumor; D005260:Female; D014453:Glucuronosyltransferase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D010597:Pharmacogenetics; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology / Q000627:therapeutic use*; D013629:Tamoxifen / Q000494:pharmacology / Q000627:therapeutic use*
D018931:Antineoplastic Agents, Hormonal; D020845:Selective Estrogen Receptor Modulators; D013629:Tamoxifen; D014453:Glucuronosyltransferase