Metformin Applications in Endometrial and Ovarian Cancer Treatment

Metformin, a first-line agent for type 2 diabetes, has emerged as a promising adjuvant in the management of endometrial and ovarian malignancies. Its antineoplastic properties arise from the activation of AMP-activated protein kinase (AMPK), leading to downstream inhibition of the mammalian target of rapamycin (mTOR) pathway, cell cycle arrest and induction of autophagy and apoptosis. By reducing circulating insulin and insulin-like growth factor signalling, metformin mitigates hyperinsulinaemia-driven tumour proliferation. In endometrial cancer models, metformin restores hormonal balance, reverses aberrant glucose and lipid metabolism and decreases markers of proliferation such as Ki-67. In ovarian cancer, mechanistic studies demonstrate its capacity to target cancer stem cells (CSCs), reprogramme the tumour microenvironment and enhance chemosensitivity to platinum agents. Beyond direct cytostatic effects, metformin modulates epigenetic regulators, including non-coding RNAs, and alleviates immunosuppressive features, thereby potentiating emerging immunotherapies. Epidemiological analyses support improved progression-free and overall survival among diabetic patients receiving metformin, although its preventive benefit remains under investigation. Collectively, these multifaceted actions position metformin as a candidate for combination regimens aimed at overcoming resistance, preserving fertility in early disease and improving outcomes across diverse patient subgroups.

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Metformin Applications in Endometrial and Ovarian Cancer Treatment publication trend

The graph below shows the total number of articles in metformin applications in endometrial and ovarian cancer treatment across all publications each year (not limited to Nature Index journals).

Technical terms

AMP-activated protein kinase (AMPK): A cellular energy sensor that, when activated, inhibits anabolic pathways and promotes catabolic processes to restore energy balance.

Mammalian target of rapamycin (mTOR): A kinase central to cell growth and proliferation; its inhibition can induce cell cycle arrest and autophagy.

Cancer stem cells (CSCs): A subpopulation of tumour cells with self-renewal capacity and resistance to conventional therapies, implicated in relapse and metastasis.

Epithelial–mesenchymal transition (EMT): A biological programme in which epithelial cells acquire mesenchymal traits, increasing motility and invasiveness.

Hyperinsulinaemia: A metabolic state characterised by excess circulating insulin, which can promote mitogenic signalling in hormone-sensitive tissues.

References

1. Glucose metabolic reprogramming and its therapeutic potential in obesity-associated endometrial cancer. Journal of Translational Medicine (2023).
2. Metformin Downregulates the Insulin/IGF-I Signaling Pathway and Inhibits Different Uterine Serous Carcinoma (USC) Cells Proliferation and Migration in p53-Dependent or -Independent Manners. PLOS ONE (2013).
3. Antiproliferative and metabolic effects of metformin in a preoperative window clinical trial for endometrial cancer. Cancer Medicine (2014).
4. Metformin inhibits estrogen‐dependent endometrial cancer cell growth by activating the AMPK–FOXO1 signal pathway. Cancer Science (2016).
5. Metformin impairs growth of endometrial cancer cells via cell cycle arrest and concomitant autophagy and apoptosis. Cancer Cell International (2014).
6. Phase II clinical trial of metformin as a cancer stem cell-targeting agent in ovarian cancer. JCI Insight (2020).
7. Enhancing Immunotherapy in Ovarian Cancer: The Emerging Role of Metformin and Statins. International Journal of Molecular Sciences (2023).
8. Mechanisms of Regulation of the Expression of miRNAs and lncRNAs by Metformin in Ovarian Cancer. Pharmaceuticals (2023).
9. Effect of metformin use on the risk and prognosis of endometrial cancer: a systematic review and meta-analysis. BMC Cancer (2018).