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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