Onkologie. 2010:4(5):326-331

Pharmacogenomical prediction of the effect of taxifen in the treatment of hormonal-dependent post-menopausal

Soňa Argalácsová¹, Ondřej Slanař², Luboš Petruželka¹

¹ Onkologická klinika VFN a 1. LF UK v Praze

² Ústav klinické biochemie a laboratorní diagnostiky VFN a Ústav farmakologie 1. LF UK v Praze

women with breast cancer based on the correlation of CYP 2D6 activity determined from the polymorphism

assessment of its gene and the analysis of gene MDR-1 for P-glycoprotein and concomitant mediaction

The initial stages of breast cancer are well treatable nowadays, provided the therapy is appropriate. Hormonal therapy is one of the

basic therapeutic modalities for the hormone- dependent breast cancer. Tamoxifen had been the first choice of therapy in hormonedependent

postmenopausal women with breast cancer till lately. The last consensus prefers selective inhibitors of aromatase (IA) in the

postmenopausal adjuvant hormonal therapy. A certain percentage of patiens continue in started therapy with tamoxifen. Metabolism

of tamoxifen in the organism – his change into active substance endoxifen and the ability to utilize tamoxifen is the function of activity

of several enzymes. The main enzyme, important duing the change from prodrug tamoxifen into its active substance endoxifen is CYP

2D6 – the member of the cytochrome P450 family. The next important part of tamoxifen metabolism and its transport into intracellular

compartment is P-glycoprotein. The process of tamoxifen utilisation and its effectivity could be affected by external factor – e. g. concomitant

medication with inhibitors of CYP 2D6 or internal factors – polymorfisms of genes for CYP 2D6 or MDR-1 (gene for P-glycoprotein).

In this artikle, we offer our preliminary results of several factors influencing the effect of tamoxifen, extended with new, yet unexplored

factor – polymorfism of MDR-1.

Keywords: AmpliChip, Tamoxifen, Molecular diagnosis, CYP2D6, MDR-1, P-glycoprotein, Concomitant medication (Comediaction), Farmacogenomic

Published: December 31, 2010  Show citation