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  • Review Article
  • Published:

Beyond aspirin—cancer prevention with statins, metformin and bisphosphonates

Nature Reviews Clinical Oncology volume 10, pages 625–642 (2013)Cite this article

Subjects

Key Points

  • Chemoprevention is a developing supplemental approach to promote cancer prevention, especially in high-risk populations

  • Studying commonly used drugs as candidate cancer chemopreventive agents has the advantage of usually having a low-risk profile and is associated with much clinical experience

  • Statins, bisphosphonates and metformin have all shown a promising degree of anticancer activity in several tumour sites

  • Evidence accumulated thus far is mostly mechanistic or from association studies in humans; data from randomized controlled trials are still lacking

  • The use of these agents for cancer chemoprevention is not yet formally indicated; however, it could be considered in high-risk populations especially if supporting pharmacogenetic markers of efficacy are available

Abstract

Cancer risk reduction using pharmacological means is an attractive modern preventive approach that supplements the classical behavioural prevention recommendations. Medications that are commonly used by large populations to treat a variety of common, non–cancer–related, medical situations are an attractive candidate pool. This Review discusses three pharmacological agents with the most evidence for their potential as cancer chemopreventive agents: anti–hypercholesterolaemia medications (statins), an antidiabetic agent (metformin) and antiosteoporosis drugs (bisphosphonates). Data are accumulating to support a significant negative association of certain statins with cancer occurrence or survival in several major tumour sites (mostly gastrointestinal tumours and breast cancer), with an augmented combined effect with aspirin or other non–steroidal anti–inflammatory drugs. Metformin, but not other hypoglycaemic drugs, also seems to have some antitumour growth activity, but the amount of evidence in human studies, mainly in breast cancer, is still limited. Experimental and observational data have identified bisphosphonates as a pharmacological group that could have significant impact on incidence and mortality of more than one subsite of malignancy. At the current level of evidence these potential chemopreventive drugs should be considered in high–risk situations or using the personalized approach of maximizing individual benefits and minimizing the potential for adverse effects with the aid of pharmacogenetic indicators.

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Figure 1: Mevalonate pathway, statins and aminobisphosphonates.
Figure 2: Proposed molecular mechanisms of the anticancer effect of metformin.
Figure 3: Bisphophonates anticancer effect.

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Both authors researched data for article, made a substantial contribution to discussion of the content, and wrote and edited the manuscript prior to submission.

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Correspondence to Gad Rennert.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Table 1

Statins: clinical studies mostly evaluating cancer as a secondary outcome of interest beyond cardiovascular events, and registry-based studies (PDF 3633 kb)

Supplementary Table 2

In vitro mechanistic studies of possible modes of action of statins (PDF 1438 kb)

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Gronich, N., Rennert, G. Beyond aspirin—cancer prevention with statins, metformin and bisphosphonates. Nat Rev Clin Oncol 10, 625–642 (2013). https://doi.org/10.1038/nrclinonc.2013.169

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