Östrojenle indüklenen meme kanseri, tedavi yaklaşımları ve melatoninin tedavideki rolü

Abstract

Supporting Institution

TÜBİTAK

Project Number

117S065

Estrogen-Induced Breast Cancer, Therapeutical Approaches and the Role of Melatonin in Treatment

Abstract

Meme kanseri, dünyada görülme sıklığı hızla artan ve kadınlarda kanserden ölüm nedenleri arasında ikinci sırada yer alan bir kanser türüdür. Endojen östrojenlerin ve bazı eksojen östrojenik bileşiklerin reseptör aracılığıyla hücre proliferasyonunu arttırarak, ya da metabolizmaları sonucu oluşan reaktif kinon metabolitlerinin DNA’ya bağlanması ile meme kanserinin oluşum ve gelişimine katkıda bulunduğu bildirilmektedir. Hormon bağımlı meme kanserinin adjuvan tedavisinde östrojenin etkisini ortadan kaldırmayı amaçlayan mekanizmalar aracılığı ile iki temel terapötik ajan grubu kullanılmaktadır; östrojenin reseptörü aracılığıyla gerçekleşen etkilerini hedef alan selektif östrojen reseptör modülatörleri (SERM) ve östrojen sentezinde yer alan enzimatik yolakları hedef alan selektif östrojen enzim modülatörleri (SEEM). Bu ilaçların çeşitli yan etkilerinin olması ve tedavi sırasında bazı ilaçlara direnç gelişmesi gibi faktörler meme kanseri tedavisinde yeni ajanların geliştirilmesi konusundaki çalışmaların sürmesini desteklemektedir. Endojen bir hormon olan melatoninin hormon-ilişkili meme kanserinde östrojen reseptörü aracılıklı etkileri değiştirdiği ve dokularda lokal östrojen sentezini inhibe ettiği bilinmektedir. Meme kanserinin önlenmesi ve tedavisinde destekleyici ajan olarak kullanımının diğer ilaçların etkinliğini artırdığı ve yan etkilerini azalttığı gösterilmiştir. Bunun yanında düşük yarılanma ömrüne sahip olması ve oral biyoyararlanımının düşük olması melatoninin ilaç olarak kullanımı kısıtlamaktadır. Bu nedenlerle yarılanma ömrü daha uzun ve daha etkin melatonin analoglarının sentezlenmesinin tedavi başarısını artırabileceği tartışılmaktadır.

Keywords

• Meme kanseri,, östrojen,SERM,SEEm,Melatonin

Project Number

117S065

References

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