Effective molecular mechanisms of resistance to cisplatin

Year 2013, Volume: 20 Issue: 2, 72 - 79, 30.06.2013

Vildan Bozok Çetintaş , Zuhal Eroğlu

Abstract

Effective molecular mechanisms of resistance to cisplatinCisplatin is a platinating chemotherapeutic agent widely used in the treatment of many solid tumors. It wasdiscovered for the first time as a growth inhibitor of Escherichia coli in 1970, later years its anticancer effectsrediscovered and began to use in the treatment of testicular, ovarian, cervical, head and neck, non-small celllung cancers and lymphoma. Although a good response to cisplatin can be achieved in the treatment oftesticular cancer, therapeutic efficacy is limited due to toxicity or drug resistance in other solid tumors. Inthis review the molecular mechanisms trough the development of cisplatin resistance and the new treatmentstrategies were evaluated. Understanding the molecular mechanisms of cisplatin resistancewill providesimportant insights for designingmore efficient platinum-based chemotherapeutics

Keywords

Cisplatin resistance, DNA damage, DNA repair, translesion synthesis, apoptosis

CİSPLATİN DİRENCİNDE ETKİLİ MOLEKÜLER MEKANİZMALAR

Abstract

Cisplatin birçok solid tümörün tedavisinde sıklıkla kullanılan platin bileşiği bir kemoterapotik ajandır. İlk defa 1970 yılında Escherichia coli' nin büyüme inhibitörü olarak keşfedilmiş, daha sonraki yıllarda anti kanser etkisi fark edilerek testis, over, serviks, baş ve boyun, küçük hücreli dışı akciğer ve lenfoma tedavisinde kullanılmaya başlanmıştır. Testis kanserlerinde cisplatine genellikle iyi yanıt alınabilmesine karşılık diğer solid tümörlerde toksisite veya ilaç direnci nedeniyle terapötik etkinlik sınırlı kalmaktadır. Bu derlemede cisplatin yanıtının oluşmasını sağlayan biyokimyasal yolaklar, direnç gelişiminde etkili moleküler mekanizmalar ve yeni tedavi stratejileri değerlendirilmiştir. Cisplatin direnci gelişimindeki moleküler mekanizmaların anlaşılması daha efektif platin bazlı kemoterapotiklerin geliştirilmesi için önemli bilgiler sağlayacaktır.

Keywords

Cisplatin direnci, DNA hasarý, DNA onarýmý, translezyon sentezi, apoptoz

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