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

Philip Lazarus; Dongxiao Sun

doi:10.3109/03602530903208652

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

Journal article

Open access

Peer reviewed

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

Philip Lazarus and Dongxiao Sun

Drug metabolism reviews, Vol.42(1), pp.182-194

02/2010

DOI: https://doi.org/10.3109/03602530903208652

Handle:

https://hdl.handle.net/2376/110017

PMCID: PMC3072888

PMID: 19821643

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Abstract

Pharmacogenetics

Humans

Receptors, Estrogen - antagonists & inhibitors

Clinical Trials as Topic

Breast Neoplasms - drug therapy

Breast Neoplasms - prevention & control

Antineoplastic Agents, Hormonal - therapeutic use

Tamoxifen - therapeutic use

Female

Androstadienes - therapeutic use

Drug Therapy, Combination

Aromatase Inhibitors - therapeutic use

Nitriles - therapeutic use

Triazoles - therapeutic use

Tamoxifen (TAM) is a selective estrogen-receptor modulator that is widely used in the prevention and treatment of estrogen-receptor-positive 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 in the 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. Aromatase inhibitors (AIs) have emerged as a viable alternative to TAM, working by inhibiting aromatase activity and blocking estrone/estrodiol biosynthesis in postmenopausal women. The current third-generation AIs, anastrozole, exemestane, and letrozole, were used initially for the treatment of metastatic breast cancer, demonstrating similar or greater benefit but less toxicity, compared with TAM, and are now being employed as adjuvant treatment for early breast cancer in postmenopausal women. This article will focus on the UDP-glucuronosyltransferases, a family of metabolizing enzymes that play an important role in the deactivation and clearance of TAM, anastrazole, and exemestane, and how interindividual differences in these enzymes may play a role in patient response to these agents.

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Title: Potential role of UGT pharmacogenetics in cancer treatment and prevention: focus on tamoxifen and aromatase inhibitors
Creators: Philip Lazarus - Departments of Pharmacology, Penn State University College of Medicine, Hershey, Pennsylvania 17033, USA. plazarus@psu.edu
Dongxiao Sun
Publication Details: Drug metabolism reviews, Vol.42(1), pp.182-194
Academic Unit: Pharmaceutical Sciences, Department of
Publisher: England
Grant note: R01 DE013158 / NIDCR NIH HHS R01 DE013158-10 / NIDCR NIH HHS R01-DE13158 / NIDCR NIH HHS
Identifiers: 99900547159401842
Language: English
Resource Type: Journal article