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.
Highlights
The nature presented itself as a potential drug resource for scientists enabling serendipitous discoveries for centuries
The venture of drug discovery has started with random screening of crude plants such as reserpine, lavender, and opium, and latterly created the drug industry, which is the one of the most advanced industries in our society (Giridhar, 2012)
In the context of drug discovery, this review focuses on non-cancer drugs that are repurposed to be used as potential prostate cancer (PCa) therapeutics
Summary
The nature presented itself as a potential drug resource for scientists enabling serendipitous discoveries for centuries. As a part of this industry, the drug discovery process had enormous investments into infrastructures. Translation of the promising molecule to Abbreviations: AR, androgen receptor; CMT, chemically modified tetracycline; CRPC, castration-resistant prostate cancer; DR, drug repositioning; EMT, epithelial-to-mesenchymal transition; ER, endoplasmic reticulum; HDAC, histone deacetylases; HMG-CoA, 3-hydroxy-3-methylglutaryl; JHCCL, Johns Hopkins Clinical Compound Library; MMP, matrix metalloproteinases; NCGC, National Health Institute Chemical Genomics Center; NPC, NCGC pharmaceutical collection; NSAID, non-steroidal anti-inflammatory drug; PCa, prostate cancer; PSA, prostate-specific antigen; VPA, valproic acid; ZA, zoledronic acid. Repurposing Non-cancer Drugs for Prostate Cancer an approved drug has major problems including high failure rates and withdrawal risks by reason of safety or efficacy problems (Shim and Liu, 2014; Würth et al, 2016)
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