Jinekolojik kanserlerin gelişiminde etkili temel moleküler mekanizmalar

Abstract

Kanserler hücrelerin çoğalma, gelişme ve ölümü arasındaki denge bozukluğuna bağlı ortaya çıkarlar. Normal bir hücrenin genetiğinin bozulması ile kontrolsüz bir şekilde bölünen kanser hücresine dönüşme süreci karsinogenez olarak adlandırılır. Salt karsinogenezde değil, metastaz oluşumu ve tedavi duyarlılığında da çeşitli moleküler mekanizmaların rol oynadığı anlaşılmıştır. Malign tümörlerin çoğunda hücre siklusunda önemli işlevleri olan protoonkogenler, tümör supresör genleri veya DNA tamir genlerinde çeşitli mutasyonlar saptanmıştır. Çoğu kanser hücresi genetik olarak kararsız olduğundan invazyon ve metastaz gibi agresif davranışlara yol açan mutasyonlar da karsinogenez süresince birikmektedir. Söz konusu moleküler değişikliklerin varlığı tümörler için hedefe yönelik veya kişiselleştirilmiş tedavi denilen farklı tedavi seçenekleri geliştirilmesine olanak vermektedir. Ayrıca tümörlerde, tümör mutasyon yükü, mikrosatellit kararsızlığı ve homolog rekombinasyon eksikliğinin değerlendirilmesiyle de ayırıcı tanı ve tedaviye katkı sağlayacak seçenekler yaratılabilmektedir. Onkolojinin diğer alanlarıyla karşılaştırıldığında jinekolojik onkoloji, genetiğe dayalı kişiselleştirilmiş tıbbı tedavilerin en zayıf kaldığı alanlardan biridir. Bu derlemede günümüze dek saptanan jinekolojik kanserlerin gelişmesinde etkili moleküler mekanizmalar, tedavide kullanılan ilaçların etkinliği ve tedavide kullanılabilecek yeni hedefe yönelik tedavi seçenekleri irdelenmiştir.

Keywords

• Jinekolojik kanserler
• Moleküler mekanizmalar
• Karsinogenez
• Hedefe yönelik tedaviler.

Basic molecular mechanisms effective in the development of gynecological cancers

Abstract

Cancers occur due to an imbalance between cell proliferation, development, and death. Carcinogenesis is the process of turning a normal cell into a cancer cell that divides uncontrollably by genetic deterioration. It has been understood that various molecular mechanisms play a role not only in carcinogenesis but also in metastasis formation and treatment sensitivity. Various mutations have been detected in proto-oncogenes, tumor suppressor genes, or DNA repair genes, which have important functions in the cell cycle in most malignant tumors. Since most cancer cells are genetically unstable, mutations that lead to aggressive behavior such as invasion and metastasis accumulate during carcinogenesis. The presence of these molecular changes allows the development of different treatment options for tumors, called targeted or tailored therapy. In addition, options that will contribute to differential diagnosis and treatment can be created by evaluating tumor mutation burden, microsatellite instability, and homologous recombination deficiency in tumors. Compared to other areas of oncology, gynecological oncology is one of the areas where genetics-based personalized medical treatments are weakest. In this review, the molecular mechanisms effective in the development of gynecological cancers detected to date, the effectiveness of drugs used in treatment, and new targeted treatment options that can be used in treatment are examined.

Keywords

• Gynecological cancers
• Carcinogenesis
• Molecular mechanisms
• Targeted therapies.

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