Drug Repositioning for Effective Prostate Cancer Treatment

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.

Identification of the targeted therapeutic potential of doxycycline for a subset of gastric cancer patients

“…18 The repurposed drugs, such as nelfinavir and digoxin, are under investigation in combination with other chemotherapeutic candidates for pancreatic cancer. 19 In the current study, we set out to identify ERK/MAPK pathway-targeting inhibitors from a set of existing drugs for possible targeted therapeutics of gastric cancer. Using a gastric cancer cell line-based ERK/ELK reporter assay, multiple classes of antibiotics were found to inhibit the ERK/MAPK pathway, and among them doxycycline was found to be very effective.…”

Drug repositioning in cancer: The current situation in Japan

“…Activity‐based DR involves testing of actual drugs using in vitro or in vivo assays . Two public comprehensive drug libraries (ie, Johns Hopkins Clinical Compound Library (JHCCL) and NCGC Pharmaceutical Collection [NPC]) are often used for drug screening in these assays.…”

“…Zoledronic acid, a bisphosphonate, is clinically used to treat osteoporosis and cancer‐related hypercalcemia and prevents skeletal complications due to bone metastases . Moreover, zoledronic acid inhibits osteoclastic bone resorption through negative regulation of the action of the farnesyl pyrophosphate synthase enzyme in the mevalonate pathway . Zoledronic acid has anticancer effects by inhibiting cell proliferation, adhesion, invasion, angiogenesis and bone metastases, and shows immunomodulatory effects, possibly through inhibition of both the Ras/mitogen‐activated protein kinase and Akt/mammalian target of rapamycin (mTOR) pathways …”

Exploring the new horizons of drug repurposing: A vital tool for turning hard work into smart work

“…The first cases of repurposing where mainly by serendipity. Then similar disease conditions which shared altered pathways were explored for combination treatment and to repurpose the drug for its treatment, instead of the originally targeted disease [181].…”