Metformin Applications in Hematologic Malignancies
Summary
Metformin, a well-established oral agent for type 2 diabetes, has attracted significant attention as an adjuvant in the treatment of hematologic malignancies. Its principal anti-neoplastic mechanism involves activation of AMP-activated protein kinase (AMPK), which in turn inhibits the mechanistic target of rapamycin (mTOR) pathway, leading to cell-cycle arrest and enhanced autophagy and apoptosis in leukaemia, lymphoma and myeloma cells. Beyond AMPK-dependent effects, metformin impairs mitochondrial complex I, reduces oxidative phosphorylation, lowers intracellular glucose flux and diminishes circulating insulin and insulin-like growth factor-1 levels that fuel tumour growth. Preclinical models demonstrate its capacity to sensitize resistant cells to cytotoxic chemotherapy and targeted therapies, while retrospective clinical analyses in diabetic cohorts receiving front-line regimens report improved progression-free and overall survival. The global significance of repurposing metformin lies in its favourable safety profile, low cost and potential to overcome drug resistance, offering a scalable strategy to enhance outcomes in diverse healthcare settings.
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Metformin Applications in Hematologic Malignancies publication trend
The graph below shows the total number of articles in metformin applications in hematologic malignancies across all publications each year (not limited to Nature Index journals).
Technical terms
AMPK: Adenosine monophosphate-activated protein kinase, an enzyme that monitors and regulates cellular energy status.
mTOR: Mechanistic target of rapamycin, a kinase central to cell growth, proliferation and metabolism.
Apoptosis: Programmed cell death involving organised dismantling of cellular components.
Autophagy: Lysosome-mediated degradation of intracellular constituents to maintain homeostasis under stress.
Chemosensitisation: Enhancement of tumour cell responsiveness to chemotherapeutic agents.
References
- Research Progress on the Use of Metformin in Leukemia Treatment. Current Treatment Options in Oncology (2024).
- Action Mechanism of Metformin and Its Application in Hematological Malignancy Treatments: A Review. Biomolecules (2023).
- Metformin sensitizes therapeutic agents and improves outcome in pre-clinical and clinical diffuse large B-cell lymphoma. Cancer & Metabolism (2020).
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