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Recently many new approaches for repurposing or repositioning of the clinically used drugs have been developed. Drug repurposing allows not only to use known schemes for the synthesis of biologically active compounds, but also to avoid multiple studies that are necessary for drug approval process – analysis of pharmacokinetics, carcinogenicity, acute and chronic toxicity, including cardiotoxicity, nephrotoxicity, allergenicity etc. It makes possible to reduce the number of experimental studies as well as costs of investigations. In cancer research drug repurposing includes screening for medicines used nowadays for the treatment of patients with non-cancer diseases which possess anticancer activity or able to enhance the effects of the standard anticancer chemotherapy, and search for new applications of known anticancer drugs for the treatment of different cancer types. Scientific rationale for the search of the compounds with potential anticancer properties among drugs with different applications is based on the multiple cross-talks of signaling pathways, which can inhibit cell proliferation. Modern advances in genomics, proteomics and bioinformatics, development of permanently improving databases of drug molecular effects and high throughput analytical systems allow researchers to analyze simultaneously a large bulk of existing drugs and specific molecular targets. This review describes the main approaches and resources currently used for the drug repurposing, as well as a number of examples.

Glucocorticoids (GCs) are often used as an adjuvant therapy to reduce the adverse effects of chemotherapy in breast cancer patients. Moreover, GCs can display pro-proliferative or anti-proliferative effects on BC cells depending on their molecular subtype. In addition, long-term use of GCs can induce drug resistance and tumor progression. The biological activity of GCs is mediated by glucocorticoid receptor (GR) via either transrepression or transactivation. The anti-inflammatory effects of GCs are thought to be due to transrepression, while side effects, drug resistance and tumor progression/metastasis are associated with transactivation. We have previously demonstrated that Compound A, a selective GR agonist (SEGRA), has a GR-dependent antitumor effect on blood cancer cells in vitro, not triggering the GR transactivation. This study was focused on the analysis of the CpdA activity in BC models in vitro. We demonstrated the antiproliferative effect of CpdA on BC cells and its ability to induce transrepression of GR-depended genes such as CCND1-3, COX-2, iNOS without the induction of transactivation. A comparative analysis showed that CpdA was an effective and safe alternative to dexamethasone in adjuvant chemotherapy for breast cancer.

Curaxins represent low molecular weight carbazole derivatives, which simultaneously activate p53-dependent apoptosis and inhibit NF-kBdependent signal transduction pathways. Antitumor activity of curaxin CBL0137 was demonstrated in vivo on the model of solid transplantable mouse colon adenocarcinoma Akatol. Significant tumor growth inhibition caused by CBL0137 treatment was observed. On the 37th day after tumor transplantation for CBL0137 oral doses 5, 10, 15 and 20 mg/kg the tumor growth inhibition indexes were 53, 50, 56 and 74 %, respectively. CBL0137 treatment extended life span of mice in all study groups receiving this test article. Maximum lifespan increase (81,7 %) was observed in the group of mice treated with 20 mg/kg dose of CBL0137. The cytotoxicity of CBL0137 was assessed on human colon cancer cells in vitro. We demonstrated that CBL0137 inhibits the expression COX2, which in its turn is known to exhibit antiapoptotic, pro-angiogenic and pro- metastatic properties. Thus, we demonstrated antitumor effect of CBL0137 against colon cancer in vitro and in vivo.