Metformin Applications in Lung Cancer Treatment

Metformin, a well-established biguanide used in the management of type 2 diabetes, has emerged as a promising adjuvant in lung cancer therapy. A growing body of preclinical and clinical evidence indicates that metformin exerts anti-tumour effects through multiple mechanisms: activation of the energy sensor AMPK leading to inhibition of mTORC1, suppression of mitochondrial oxidative phosphorylation, and disruption of aberrant metabolic programmes such as lactate overproduction. Beyond metabolic reprogramming, metformin has been shown to inhibit epithelial–mesenchymal transition, enhance DNA damage induced by platinum-based drugs, and overcome acquired chemoresistance. Retrospective analyses in diabetic patient cohorts suggest an association between metformin use and improved survival in non-small cell and small cell lung cancers. Ongoing efforts aim to define biomarkers of response, such as LKB1 status, and to optimise dosing schedules in combination with chemotherapy, targeted agents or radiotherapy. The global significance of repurposing metformin lies in its favourable safety profile, low cost and potential to broaden therapeutic options for a disease with persistently high mortality.

Research from Nature Portfolio

Recent studies have demonstrated that metformin enhances the radiosensitising effect of cisplatin in non-small cell lung cancer cell lines with differing cisplatin sensitivities. Treatment with metformin plus cisplatin and ionising radiation increased the formation of cisplatin-DNA adducts and downregulated the excision repair enzyme ERCC1, leading to prolonged persistence of radiation-induced DNA damage foci. Mechanistic investigations revealed that an AMPK-dependent pathway mediates this radiosensitisation in one cell line background, while alternative routes prevail in another, highlighting the need for genotype-guided combination strategies.

Metformin Applications in Lung Cancer Treatment publication trend

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

Technical terms

AMP-activated protein kinase (AMPK): A central cellular energy sensor that, when activated by increased AMP/ATP ratio or pharmacological agents such as metformin, inhibits anabolic processes and promotes catabolism.

mTORC1: Mammalian target of rapamycin complex 1, a key regulator of cell growth and protein synthesis; its inhibition can suppress tumour proliferation.

Epithelial–Mesenchymal Transition (EMT): A process by which epithelial cells acquire mesenchymal properties, enhancing motility and invasiveness—a critical step in metastasis.

References

1. AMPK: An energy sensor for non-small cell lung cancer progression and treatment. Pharmacological Research (2025).
2. Dietary Folate Deficiency Promotes Lactate Metabolic Disorders to Sensitize Lung Cancer Metastasis through MTOR-Signaling-Mediated Druggable Oncotargets. Nutrients (2023).
3. Metformin in Lung Cancer: Review of in Vitro and in Vivo Animal Studies. Cancers (2017).
4. Understanding the benefit of metformin use in cancer treatment. BMC Medicine (2011).
5. Metformin Inhibits the IL-6-Induced Epithelial-Mesenchymal Transition and Lung Adenocarcinoma Growth and Metastasis. PLOS ONE (2014).
6. LKB1/AMPK/mTOR Signaling Pathway in Non-small-cell Lung Cancer. Asian Pacific Journal of Cancer Prevention (2013).
7. Metformin use and its effect on survival in diabetic patients with advanced non-small cell lung cancer. BMC Cancer (2016).
8. Metformin therapy associated with survival benefit in lung cancer patients with diabetes. Oncotarget (2016).
9. Metformin enhances the radiosensitizing effect of cisplatin in non-small cell lung cancer cell lines with different cisplatin sensitivities. Scientific Reports (2019).