Moleküler Hedefli Anti-Kanser Ajan Kombinasyonlarını Optimize Etmek İçin Stratejiler

Kanser kemoterapisinde kullandığımız sitotoksik ajanlar, neoplastik hücrelerin sayılarını birkaç kat azalmakta, ancak tam olarak yok edememektedir. Bu nedenle solid kanserli hastalarda çok daha rasyonel yaklaşımla geliştirilmiş olan ‘hedeflenmiş terapötikler’in kullanımları belirgin bir şekilde artmaktadır. Hedeflenmiş terapötikler ‘seçici hedefleri’ nedeniyle ‘özgül-moleküler defekti’ olan tümor hücrelerine yönelerek kanser hücresini öldürürken normal hücrelerin sağlıklı bir ortamda devamına imkan tanımaktadır. Kansere özgü moleküler hedeflerin sürekli büyüyen listesini modüle eden yüzlerce yeni ajanların hızla ortaya çıkması kanser hastaları için büyük umut vaat etmektedir. Hedef ajanların tek olarak, standart tedaviler ile ve diğer hedef ajanları ile kombinasyonlarının değerlendirilmesi önemli gelişim zorluklarını da beraberinde getirmektedir. Olası ilaç kombinasyonlarının sayısı gerçekte sınırsız olduğundan, en umut verici kombinasyonların belirlenmesine ve bunların değerlendirilmesine öncelik verecek olan stratejiler çok önemlidir. Burada, hedef ajan kombinasyonlarının gelişim stratejilerinin önemli unsurları dikkate alınacaktır. Bu tür kombinasyonların rasyonel pre-klinik ve klinik değerlendirmelerindeki zorluklar ve bu zorlukların üstesinden gelmek için olası yaklaşımlar gözden geçirilecektir

Anahtar Kelimeler:

Moleküler hedefli anti-kanser ajanları, kanser tedavi hedefleri

Strategies to Optimize the MolecularlyTargeted Anti-Cancer Agent Combinations

Cytotoxic agents which are used in cancer chemotherapy reduced several times the number of neoplastic cells but not fully. Therefore, usage of “targeted therapeutics" which were developed with much more rational approach is increasing markedly in patients with solid cancer. Targeted therapeutics due to 'selective targets' aims cancer cells with specific molecular defect thereby, kils the cancer cells, which makes it possible to continue normal cells in a healthy environment. The rapid emergence of hundreds of new agents that modulates ever-growing list of the cancer-specific molecular targets promise great hope for cancer patients. Evaluation of the target agent individually, in combination with standard therapy and other target agents bring about important development challenges. As possible combinations of drugs number is unlimited, the identification of the most promising combinations and giving priority to assessing their strategies are very important.In this article important elements of the development strategy of the target agent combinations will be considered. Difficulties in this kind of combinations of rational pre-clinical and clinical evaluation and possible approaches to overcome these challenges will be discussed.

Keywords:

Molecularly targeted anti-cancer agents, cancer therapeutic targets,

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