Pharmacogenetics of CYP2D6 and tamoxifen therapy: Light at the end of the tunnel?

被引：29

作者：

Del Re, M. ^{[1
]}

Citi, V. ^{[1
]}

Crucitta, S. ^{[1
]}

Rofi, E. ^{[1
]}

Belcari, F. ^{[1
]}

van Schaik, R. H. ^{[2
]}

Danesi, R. ^{[1
]}

机构：

[1] Univ Hosp, Dept Lab Med, Clin Pharmacol & Pharmacogenet Unit, Pisa, Italy

[2] Erasmus MC, Dept Clin Chem, Rotterdam, Netherlands

来源：

PHARMACOLOGICAL RESEARCH | 2016年 / 107卷

关键词：

Pharmacogenetics; Breast cancer; CYP2D6; Tamoxifen; Polymorphisms; CYTOCHROME-P450; 2D6; CYP2D6; ADJUVANT ENDOCRINE THERAPY; BREAST-CANCER; ALLELIC VARIANTS; IN-VIVO; GENETIC-POLYMORPHISM; FUNCTIONAL-CHARACTERIZATION; INTERETHNIC DIFFERENCES; POSTMENOPAUSAL WOMEN; POOR METABOLIZERS;

D O I：

10.1016/j.phrs.2016.03.025

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

The clinical usefulness of assessing the enzymatic activity of CYPD6 in patients taking tamoxifen had been longly debated. In favour of preemptive evaluation of phenotypic profile of patients is the strong pharmacologic rationale, being that the formation of endoxifen, the major and clinically most important metabolite of tamoxifen, is largely dependent on the activity of CYP2D6. This enzyme is highly polymorphic for which the activity is largely depending on genetics, but that can also be inhibited by a number of drugs, i.e. antidepressants, which are frequently used in patients with cancer. Unfortunately, the clinical trials that have been published in the last years are contradicting each other on the association between CYP2D6 and significant clinical endpoints, and for this reason CYP2D6 genotyping is at present not generally recommended. Despite this, the CYP2D6 genotyping test for tamoxifen is available in many laboratories and it may still be an appropriate test to use it in specific cases. (C) 2016 Elsevier Ltd. All rights reserved.

引用

页码：398 / 406

页数：9

共 85 条

[61] Impacts of the Glucuronidase Genotypes UGT1A4, UGT2B7, UGT2B15 and UGT2B17 on Tamoxifen Metabolism in Breast Cancer Patients [J].

Romero-Lorca, Alicia ;

Novillo, Apolonia ;

Gaibar, Maria ;

Bandres, Fernando ;

Fernandez-Santander, Ana .

PLOS ONE, 2015, 10 (07)

[62]

Sachse C, 1997, AM J HUM GENET, V60, P284

[63] Functional Characterization of 17 CYP2D6 Allelic Variants (CYP2D6.2, 10, 14A-B, 18, 27, 36, 39, 47-51, 53-55, and 57) [J].

Sakuyama, Kanako ;

Sasaki, Takamitsu ;

Ujiie, Shuta ;

Obata, Kanako ;

Mizugaki, Michinao ;

Ishikawa, Masaaki ;

Hiratsuka, Masahiro .

DRUG METABOLISM AND DISPOSITION, 2008, 36 (12) :2460-2467

[64] Tamoxifen metabolism predicts drug concentrations and outcome in premenopausal patients with early breast cancer [J].

Saladores, P. ;

Muerdter, T. ;

Eccles, D. ;

Chowbay, B. ;

Zgheib, N. K. ;

Winter, S. ;

Ganchev, B. ;

Eccles, B. ;

Gerty, S. ;

Tfayli, A. ;

Lim, J. S. L. ;

Yap, Y. S. ;

Ng, R. C. H. ;

Wong, N. S. ;

Dent, R. ;

Habbal, M. Z. ;

Schaeffeler, E. ;

Eichelbaum, M. ;

Schroth, W. ;

Schwab, M. ;

Brauch, H. .

PHARMACOGENOMICS JOURNAL, 2015, 15 (01) :84-94

[65] Characterization of (±)-bufuralol hydroxylation activities in liver microsomes of Japanese and Caucasian subjects genotyped for CYP2D6 [J].

Shimada, T ;

Tsumura, F ;

Yamazaki, H ;

Guengerich, FP ;

Inoue, K .

PHARMACOGENETICS, 2001, 11 (02) :143-156

[66]

SHIMADA T, 1994, J PHARMACOL EXP THER, V270, P414

[67]

Sim Sarah C, 2013, Methods Mol Biol, V987, P251, DOI 10.1007/978-1-62703-321-3_21

[68]

Sistonen J, 2007, PHARMACOGENET GENOM, V17, P93

[69] Active tamoxifen metabolite plasma concentrations after coadministration of tamoxifen and the selective serotonin reuptake inhibitor paroxetine [J].

Stearns, V ;

Johnson, MD ;

Rae, JM ;

Morocho, A ;

Novielli, A ;

Bhargava, P ;

Hayes, DF ;

Desta, Z ;

Flockhart, DA .

JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 2003, 95 (23) :1758-1764

[70] Hot flushes [J].

Stearns, V ;

Ullmer, L ;

López, JF ;

Smith, Y ;

Isaacs, C ;

Hayes, DF .

LANCET, 2002, 360 (9348) :1851-1861

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