Metformin, Diyabet ve Meme Kanseri Üçgeni

Metformin, tip 2 diyabet (T2D) tedavisinde kullanılan umut verici, iyi bilinen bir klinik ilaçtır. Gerçekleştirilen epidemiyolojik çalışmaların meta-analizlerine göre, T2D’nin kanser gelişimiyle-özellikle meme kanserinde-insidans açısından-negatif bir korelasyonu vardır ve kanser hastaları metformin ile tedavi edildiğinde mortalite riskinin azaldığının gösterilmesi, metformin ve tümör oluşumu arasında bir bağlantı olduğunu düşündürmekte bu durumda birçok araştırmacının dikkatini çekmektedir. İlginçtir ki, sadece in vivo değil, aynı zamanda in vitro çalışmalar da metforminin direkt bir antitümör etkisine sahip olduğunu doğrulamaktadır, çünkü metformin, tümör proliferasyonunu baskılayabilir ve hücre döngüsü durmasını, apoptozunu ve hatta tümör hücrelerinin otofajisini tetikleyebilir. Bununla birlikte, metforminin kanser hücreleri üzerinde inhibe edici etkisini ortaya çıkaran kesin mekanizma henüz tam olarak belirlenmemiştir. Bu derlemede, metforminin etki mekanizması, hem T2D, hem de kanser ile ilişkili olarak değerlendirilmiştir. Kanser düzenleme yollarının detaylandırılması, metformini kanser tedavisinde yeni yaklaşımlar için bir aday olarak göstermektedir. Bu nedenle, metformin tedavisinin kanser önleme ve nüks durumunda hem tekli hem de adjuvan tedavilerde doğru etkinliğini doğrulamak için ek araştırmalara ihtiyaç vardır. Yapılacak büyük ölçekli klinik araştırmalar metforminin anti-kanser etkisini desteklerse, metformin, kanser tedavisi için umut vadeden, yeniden konumlandırılmış bir seçenek haline gelebilir.

The Triangle of Metformin, Type 2 diabetes mellitus, and the Breast Cancer

Metformin is a promising well-known clinical drug used in type 2 diabetes mellitus (T2DM) treatment. According to meta-analyses of epidemiological studies, T2DM has a negative correlation-in case of incidence- with cancer development-especially breast cancer- and that patients with cancer have decreased risk of mortality if treated with metformin, suggesting a linkage between metformin and tumorigenesis which draws the attention of many researchers. Interestingly enough, not only in vivo but also in vitro studies have confirmed that metformin has a straightforward antitumor effect, as it may suppress tumor proliferation and trigger cell cycle arrest, apoptosis, and even autophagy of tumor cells. However, the exact mechanism by which metformin produces its inhibitory effect on cancer cells has not been well established yet. Here in this review, the mechanism of action of metformin is evaluated in correlation with both T2DM and cancer. Well-established cancer regulation pathways nominate metformin as a candidate for novel approaches in cancer treatment. Thus, additional research is needed to confirm the correct efficacy of metformin therapy in both single or adjuvant therapies in case of cancer prevention and recurrence. If large-scale clinical trials support the anti-cancer effect of metformin, metformin could become a rewarding and repositioned option for cancer therapy.

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