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Review
. 2018 May 15:9:500.
doi: 10.3389/fphys.2018.00500. eCollection 2018.

Drug Repositioning for Effective Prostate Cancer Treatment

Beste Turanli  1   2   3 , Morten Grøtli  4 , Jan Boren  5 , Jens Nielsen  6 , Mathias Uhlen  1 , Kazim Y Arga  3 , Adil Mardinoglu  1   6
Affiliations
Review

Drug Repositioning for Effective Prostate Cancer Treatment

Beste Turanli et al. Front Physiol. .

Abstract

Drug repositioning has gained attention from both academia and pharmaceutical companies as an auxiliary process to conventional drug discovery. Chemotherapeutic agents have notorious adverse effects that drastically reduce the life quality of cancer patients so drug repositioning is a promising strategy to identify non-cancer drugs which have anti-cancer activity as well as tolerable adverse effects for human health. There are various strategies for discovery and validation of repurposed drugs. In this review, 25 repurposed drug candidates are presented as result of different strategies, 15 of which are already under clinical investigation for treatment of prostate cancer (PCa). To date, zoledronic acid is the only repurposed, clinically used, and approved non-cancer drug for PCa. Anti-cancer activities of existing drugs presented in this review cover diverse and also known mechanisms such as inhibition of mTOR and VEGFR2 signaling, inhibition of PI3K/Akt signaling, COX and selective COX-2 inhibition, NF-κB inhibition, Wnt/β-Catenin pathway inhibition, DNMT1 inhibition, and GSK-3β inhibition. In addition to monotherapy option, combination therapy with current anti-cancer drugs may also increase drug efficacy and reduce adverse effects. Thus, drug repositioning may become a key approach for drug discovery in terms of time- and cost-efficiency comparing to conventional drug discovery and development process.

Keywords: approved drugs; drug repositioning; non-cancer therapeutics; prostate cancer; repurposing.

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Figures

FIGURE 1
FIGURE 1
Different drug repositioning approaches for drug discovery and validation.
FIGURE 2
FIGURE 2
Chemical structures of repurposed non-cancer drug candidates for prostate cancer.
FIGURE 3
FIGURE 3
The use of system biology in the drug repositioning. (A) Potential data accumulation to be used in systems biology based approaches. (B) The application of two fundamental approaches in systems biology for drug design and discovery.
FIGURE 4
FIGURE 4
Proposed anti-cancer mechanisms of clinically evaluated repurposed drug candidates.
See this image and copyright information in PMC

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