Potential role of UGT pharmacogenetics in cancer treatment and prevention: focus on tamoxifen

Philip Lazarus; Andrea S Blevins-Primeau; Yan Zheng; Dongxiao Sun

doi:10.1111/j.1749-6632.2009.04114.x

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Potential role of UGT pharmacogenetics in cancer treatment and prevention: focus on tamoxifen

Accepted manuscript

Open access

Potential role of UGT pharmacogenetics in cancer treatment and prevention: focus on tamoxifen

Philip Lazarus, Andrea S Blevins-Primeau, Yan Zheng and Dongxiao Sun

Annals of the New York Academy of Sciences, Vol.1155(1), pp.99-111

02/2009

DOI: https://doi.org/10.1111/j.1749-6632.2009.04114.x

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https://hdl.handle.net/2376/103008

PMCID: PMC2694135

PMID: 19250197

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https://doi.org/10.1111/j.1749-6632.2009.04114.xView

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Abstract

Antineoplastic Agents, Hormonal - pharmacology

Humans

Breast Neoplasms - drug therapy

Breast Neoplasms - prevention & control

Glucuronosyltransferase - genetics

Breast Neoplasms - enzymology

Breast Neoplasms - genetics

Glucuronosyltransferase - metabolism

Selective Estrogen Receptor Modulators - therapeutic use

Antineoplastic Agents, Hormonal - therapeutic use

Tamoxifen - therapeutic use

Tamoxifen - pharmacology

Cell Line, Tumor

Female

Selective Estrogen Receptor Modulators - pharmacology

Pharmacogenetics

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.

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Title: Potential role of UGT pharmacogenetics in cancer treatment and prevention: focus on tamoxifen
Creators: Philip Lazarus - 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
Andrea S Blevins-Primeau
Yan Zheng
Dongxiao Sun
Publication Details: Annals of the New York Academy of Sciences, Vol.1155(1), pp.99-111
Academic Unit: Department of Pharmaceutical Sciences
Publisher: United States
Grant note: R01 DE013158-08 / NIDCR NIH HHS R01 DE013158 / NIDCR NIH HHS R01 DE013158-07A2 / NIDCR NIH HHS R01-DE13158 / NIDCR NIH HHS
Identifiers: 99900546678901842
Language: English
Resource Type: Accepted manuscript