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Overcoming Drug Development Bottlenecks With Repurposing: Repurposing biguanides to target energy metabolism for cancer treatment

Nature Medicine volume 20, pages 591–593 (2014)Cite this article

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Metformin is a drug commonly used for treating type 2 diabetes—yet there are more than 100 ongoing trials of metformin at conventional antidiabetic doses for cancer treatment. This situation has arisen in large part because, in contrast to newly synthesized and patented drug candidates where drug supply is controlled and clinical trials are coordinated in a central office, there is a low 'barrier to entry' to initiate a clinical trial of an inexpensive generic drug for a potential new indication. When there is an intriguing rationale and a low risk of toxicity, as is the case for treatment of cancer with metformin, many investigators launch clinical trials, but the coordination associated with conventional drug development programs is absent.

The initially proposed mechanism for antineoplastic activity of metformin is as follows, and it remains plausible. High insulin levels are associated with adverse outcomes of many cancers6, and many cancers express insulin receptors. In turn, insulin activates the phosphoinositide 3-kinase–mammalian target of rapamycin (PI3K-mTOR) signaling pathway, which favors mRNA translation, cell survival and proliferation. Metformin is known to lower the elevated insulin levels common in type 2 diabetes and hence may reduce activation of the PI3K-mTOR pathway in cancers.

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Figure 1: Repurposing metformin.

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  1. Michael Pollak is at the Department of Oncology, McGill University and Segal Cancer Centre of the Jewish General Hospital, Montreal, Quebec, Canada.,

    Michael Pollak

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  1. Michael Pollak
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Correspondence to Michael Pollak.

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Pollak, M. Overcoming Drug Development Bottlenecks With Repurposing: Repurposing biguanides to target energy metabolism for cancer treatment. Nat Med 20, 591–593 (2014). https://doi.org/10.1038/nm.3596

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