Metformin: A candidate for the treatment of gynecological tumors based on drug repositioning

Abstract

Abstract. Metformin is a first-line drug used for the treatment of type 2 diabetes. Recently, metformin has been reported to reduce the carcinogenic risk and inhibit tumor cell growth in glioma and breast cancer. The anticancer action of metformin involves the enhancement of phosphorylation of liver kinase B1, activation of adenosine monophosphate-activated protein kinase and inhibition of mammalian target of rapamycin, which reduces cell growth. Metformin is anticipated to exert antitumor effects in gynecological cancer, and its efficacy for the treatment of endometrial, breast and ovarian cancer has been suggested in preclinical studies and clinical trials. Although the effect of metformin on cervical cancer remains to be examined in clinical trials, its antitumor effects have been reported in preclinical studies. Thus, the use of metformin for the treatment of gynecological cancer may become a successful example of drug repositioning, following establishment of the drug's antitumor effects, risk evaluation, screening and validation of efficacy.

Antidiabetic Medication, Statins and the Risk and Prognosis of Non-endometrioid Endometrial Cancer in Women with Type 2 Diabetes

“…The potential anticancer properties of metformin are thought to be mediated both directly via the 5' adenosine monophosphateactivated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway and indirectly by reducing circulating glucose and insulin levels (7). Recently there has been much interest in the idea of repurposing metformin as a preventive agent and co-treatment for cancer (40), and several clinical studies on metformin and EC are ongoing despite limited scientific data available.…”

Epidemiology of ovarian cancer: a review

“…Long-term use (≥ 30 prescriptions) of metformin (and not sulfonylureas or insulin) was associated with a trend towards reduced risk (OR=0.61, 95% CI: 0.30–1.25), but the results were not statistically significant. Additional studies have observed decreased incidence and mortality among metformin treated groups 349 . Given the absence of good screening tests, the potential for use of metformin as a chemopreventive agent merits further exploration.…”

TYRO3: A potential therapeutic target in cancer

“…[174][175][176][177] The efficacy of metformin for the treatment of endometrial, cervical, breast, and ovarian cancer has been suggested in preclinical studies and clinical trials. 154 The anticancer mechanisms of metformin have been assessed by its ability to inhibit pro-survival and anti-apoptotic signals mediated by mammalian target of rapamycin complex 1, EGFR, and MAPK. [178][179][180][181] Metformin may target TYRO3 to prevent cell proliferation and reduce chemoresistance.…”