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Drug Repositioning for Effective Prostate Cancer Treatment

Journal article
Authors B. Turanli
Morten Grötli
Jan Borén
J. Nielsen
M. Uhlen
K. Y. Arga
A. Mardinoglu
Published in Frontiers in Physiology
Volume 9
ISSN 1664-042X
Publication year 2018
Published at Department of Chemistry and Molecular Biology
Institute of Medicine, Department of Molecular and Clinical Medicine
Language en
Keywords prostate cancer, drug repositioning, non-cancer therapeutics, repurposing, approved drugs, cell lung-cancer, valproic acid, zoledronic acid, anticancer agent, phase-ii, in-vivo, repurposing itraconazole, cardiac-glycosides, antitumor-activity, aldose reductase
Subject categories Cancer and Oncology

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-kappa B inhibition, Wnt/beta - Catenin pathway inhibition, DNMT1 inhibition, and GSK-3 beta 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.

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