Tamoksifenle Tedavi Edilen Meme Kanser Hastalarında CYP 2D6 Genetik Polimorfizminin Önemi

Yıl 2018, Cilt: 6 Sayı: 2, 30 - 39, 04.02.2018

Selina Toplayıcı

Öz

Öz

Tamoksifen östrojen reseptör pozitif meme kanser hastalarının tedavisinin temel taşını oluşturmaktadır. Tamoksifenin etkinliği biyotransformasyonuna bağımlıdır. Biyotransformasyonu baskın olarak CYP 2D6 izoformu tarafından gerçekleştirilerek, tamoksifen aktif metaboliti olan endoksifene dönüştürülmektedir. Hem genetik hem de çevresel faktörler CYP 2D6 enzim aktivitesini değiştirebilmekte, bu durumda aktif tamoksifen metabolitlerinin konsantrasyonlarını direkt olarak etkileyebilmektedir. Çok sayıda çalışmada, CYP 2D6 genetik varyantlarının adjuvant tamoksifenle tedavi edilen hastaların klinik sonuçlarını etkileyebileceği gösterilmiştir. Kişiye özel tedavi uygulamalarında, CYP 2D6 genotipleri ve TAM tedavisinin klinik yanıtı arasındaki bağlantı özellikle meme kanser hastalarında yoğun bir şekilde araştırılmaktadır. Derlememizde tamoksifenin tedavi yanıtıyla ilişkilendirilen CYP 2D6 genetik polimorfizminin moleküler dinamiğini ve klinikteki önemini özetlemeye çalıştık. Bu bilgilerin diğer çalışmalara ışık tutacağına inanmaktayız.

Anahtar Kelimeler

CYP 2D6, genetik polimorfizm, meme kanseri, tamoksifen

The İmportance Of Genetic Polymorphism Of CYP 2D6 İn Breast Cancer Patients Treated With Tamoxifen

Öz

Abstract

Tamoxifen constitutes the cornerstone of the treatment of estrogen receptor positi-ve breast cancer patients. Tamoxifen effectiveness is dependent on the biotransformation. Metabolism is predominantly carried out by the CYP 2D6 isoform and tamoksifen is converted to its active metabolit endoxifen. Both genetic and environmental factors can modify the CYP 2D6 enzyme activity, hence it can directly affect the concentrations of active metabolite of tamoxifen. In a number of studies it has shown CYP 2D6genetic variants may affect the clinical outcomes of patients treated with adjuvant tamoxifen. People in private therapy practice, the link between the CYP 2D6 genotype andthe clinical response of TAM treatment being studied intensively, especially in breast cancer patients. In this review, we tried to summarize themolecular dynamics of CYP 2D6 genetic polymorphism which is associated with tamoxifen treatment response andthe importance of the clinic. We believe this information willshed light on the other studies.

Kaynakça

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