Metformin and its derivatives in breast cancer: from glycaemic control to tumor-intrinsic pathways
Abstract
BACKGROUND: Breast cancer (BC) remains the most commonly diagnosed malignancy among women worldwide, with metabolic dysregulation of glucose and hyperinsulinemia increasingly recognised as contributors to its development and progression. However, despite accumulating evidence linking metabolic imbalances to tumorigenesis, the precise therapeutic opportunities arising from targeting these metabolic pathways remain insufficiently defined.
OBJECTIVE: To explore the potential of metformin and its derivatives, in combination with other anticancer agents, to suppress BC cell proliferation by targeting glucose metabolism.
RESULTS: Preclinical and epidemiological evidence indicates that metformin may reduce BC incidence and improve survival, with particularly pronounced benefits observed in triple-negative and Human Epidermal Growth Factor Receptor 2(HER2) positive subtypes, especially when used in combination with chemotherapy or targeted therapies. The drug's anticancer potential is mediated through both systemic and tumor-intrinsic mechanisms. Systemically, metformin enhances insulin sensitivity and suppresses hepatic glucose production, thereby lowering circulating insulin and IGF-1 levels and attenuating growth factor-driven proliferation. At the tumor level, it activates AMP-activated protein kinase, inhibits the mammalian target of rapamycin pathway, disrupts mitochondrial oxidative phosphorylation, and induces apoptosis through metabolic stress. In addition, novel biguanide…
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