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Metformin + temsirolimus is an experimental drug combination consisting of the biguanide metformin and the mTOR inhibitor temsirolimus. This combination was investigated in clinical trials led by the London Health Sciences Centre for the treatment of advanced solid tumors and lymphoma. Metformin, traditionally used as an antidiabetic agent, functions by activating AMP-activated protein kinase (AMPK), which leads to the indirect inhibition of the mammalian target of rapamycin (mTOR) pathway and a reduction in systemic insulin levels. Temsirolimus is a specific inhibitor of mTOR (specifically mTORC1), a kinase that regulates cell growth, proliferation, and survival. The therapeutic rationale for the combination is to achieve more robust inhibition of the PI3K/Akt/mTOR signaling axis, which is frequently dysregulated in various cancers, and to potentially overcome resistance mechanisms associated with single-agent mTOR inhibition.
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