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Review
. 2021 Feb 13;23(3):29.
doi: 10.1007/s11912-021-01023-z.

Statins as Potential Chemoprevention or Therapeutic Agents in Cancer: a Model for Evaluating Repurposed Drugs

Nalinie Joharatnam-Hogan  1   2 , Leo Alexandre  3   4 , James Yarmolinsky  5 , Blossom Lake  6 , Nigel Capps  6 , Richard M Martin  7   8 , Alistair Ring  9 , Fay Cafferty  10 , Ruth E Langley  10
Affiliations
Review

Statins as Potential Chemoprevention or Therapeutic Agents in Cancer: a Model for Evaluating Repurposed Drugs

Nalinie Joharatnam-Hogan et al. Curr Oncol Rep. .

Abstract

Purpose of review: Repurposing established medicines for a new therapeutic indication potentially has important global and societal impact. The high costs and slow pace of new drug development have increased interest in more cost-effective repurposed drugs, particularly in the cancer arena. The conventional drug development pathway and evidence framework are not designed for drug repurposing and there is currently no consensus on establishing the evidence base before embarking on a large, resource intensive, potential practice changing phase III randomised controlled trial (RCT). Numerous observational studies have suggested a potential role for statins as a repurposed drug for cancer chemoprevention and therapy, and we review the strength of the cumulative evidence here.

Recent findings: In the setting of cancer, a potential repurposed drug, like statins, typically goes through a cyclical history, with initial use for several years in another disease setting, prior to epidemiological research identifying a possible chemo-protective effect. However, further information is required, including review of RCT data in the initial disease setting with exploration of cancer outcomes. Additionally, more contemporary methods should be considered, such as Mendelian randomization and pharmaco-epidemiological research with "target" trial design emulation using electronic health records. Pre-clinical and traditional observational data potentially support the role of statins in the treatment of cancer; however, randomised trial evidence is not supportive. Evaluation of contemporary methods provides little added support for the use of statin therapy in cancer. We provide complementary evidence of alternative study designs to enable a robust critical appraisal from a number of sources of the go/no-go decision for a prospective phase III RCT of statins in the treatment of cancer.

Keywords: Cancer; Drug development; Drug repurposing; Statins.

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Conflict of interest statement

Nalinie Joharatnam-Hogan is funded by a CRUK Clinical Trial Fellowship grant. Leo Alexandre is funded by the National Institute of Health Research (NIHR) as a clinical lecturer. James Yarmolinsky, Blossom Lake, Nigel Capps, Richard M. Martin, Alistair Ring, and Fay Cafferty declare no conflict of interest. Ruth Langley has received research funding through grants from CRUK and NIHR, and has received honorarium from the Aspirin Foundation.

Figures

Fig. 1
Fig. 1
a Standard drug development pathway97. b Proposed drug development pathway for repurposed drugs
Fig. 2
Fig. 2
The mevalonate pathway and possible mechanism of action of statins
See this image and copyright information in PMC

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