Preview

Siberian journal of oncology

Advanced search

VARIANTS AND PERSPECTIVES OF DRUG REPURPOSING FOR CANCER TREATMENT

https://doi.org/10.21294/1814-4861-2018-17-3-77-87

Abstract

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.

About the Authors

A. V. Savinkova
N.N. Blokhin National Medical Research Center of Oncology
Russian Federation

24, Kashirskoe shosse, 115478-Moscow,Russia

Junior Researcher, Department of Chemical Carcinogenesis, N.N. Blokhin National Medical Research Center of Oncology (Moscow, Russia).  Researcher ID (WOS): K-6838-2018. Author ID (Scopus): 985189



E. M. Zhidkova
N.N. Blokhin National Medical Research Center of Oncology
Russian Federation

24, Kashirskoe shosse, 115478-Moscow,Russia

Junior Researcher, Department of Chemical Carcinogenesis, N.N. Blokhin National Medical Research Center of Oncology (Moscow, Russia)



L. R. Tilova
N.N. Blokhin National Medical Research Center of Oncology
Russian Federation

24, Kashirskoe shosse, 115478-Moscow,Russia

Postgraduate, Department of Chemical Carcinogenesis, N.N. Blokhin National Medical Research Center of Oncology (Moscow, Russia)



M. D. Lavrova
D.I. Mendeleev University of Chemical Technology of Russia
Russian Federation

9, Miusskaya sq., 125047-Moscow, Russia

Student, D.I. Mendeleev University of Chemical Technology of Russia (Moscow, Russia)



E. S. Lylova
Moscow Technological University
Russian Federation

78, Vernadsky Avenue, Moscow-119454, Russia

Student, Moscow Technological University (Moscow, Russia)



K. A. Kuzin
N.N. Blokhin National Medical Research Center of Oncology
Russian Federation

24, Kashirskoe shosse, 115478-Moscow,Russia

Junior Researcher, Department of Chemical Carcinogenesis, N.N. Blokhin National Medical Research Center of Oncology (Moscow, Russia)



A. Yu. Portyannikova
N.N. Blokhin National Medical Research Center of Oncology
Russian Federation

24, Kashirskoe shosse, 115478-Moscow,Russia

Laboratory Research Assistant, Department of Chemical Carcinogenesis, N.N. Blokhin National Medical Research Center of Oncology (Moscow, Russia)



V. P. Maximova
N.N. Blokhin National Medical Research Center of Oncology
Russian Federation

24, Kashirskoe shosse, 115478-Moscow,Russia

Junior Researcher, Department of Chemical Carcinogenesis, N.N. Blokhin National Medical Research Center of Oncology (Moscow, Russia)



A. V. Kholodova
Moscow Technological University
Russian Federation

78, Vernadsky Avenue, Moscow-119454, Russia

Student, Moscow Technological University (Moscow, Russia)



O. A. Vlasova
N.N. Blokhin National Medical Research Center of Oncology
Russian Federation

24, Kashirskoe shosse, 115478-Moscow,Russia

Junior Researcher, Department of Chemical Carcinogenesis, N.N. Blokhin National Medical Research Center of Oncology (Moscow, Russia)



T. I. Fetisov
N.N. Blokhin National Medical Research Center of Oncology
Russian Federation

24, Kashirskoe shosse, 115478-Moscow,Russia

Laboratory Research Assistant, Department of Chemical Carcinogenesis, N.N. Blokhin National Medical Research Center of Oncology (Moscow, Russia)



K. I. Kirsanov
N.N. Blokhin National Medical Research Center of Oncology
Russian Federation

24, Kashirskoe shosse, 115478-Moscow,Russia

PhD, Head of Laboratory of Chemical Carcinogens, N.N. Blokhin National Medical Research Center of Oncology (Moscow, Russia). Researcher ID (WOS): L-3062-2015. Author ID (Scopus): 184421



G. A. Belitskiy
N.N. Blokhin National Medical Research Center of Oncology
Russian Federation

24, Kashirskoe shosse, 115478-Moscow,Russia

MD, PhD, DSc, Professor, Leading Researcher, Department of Chemical Carcinogenesis N.N. Blokhin National Medical Research Center of Oncology (Moscow, Russia). Researcher ID (WOS): L-3062-2015. Author ID (Scopus): 107231



M. G. Yakubovskaya
N.N. Blokhin National Medical Research Center of Oncology
Russian Federation

24, Kashirskoe shosse, 115478-Moscow,Russia

MD, PhD, DSc, Head of Department of Chemical Carcinogenesis, N.N. Blokhin National Medical Research Center of Oncology (Moscow, Russia). Researcher ID (WOS): R-6984-2016. Author ID (Scopus): 583045



E. A. Lesovaya
N.N. Blokhin National Medical Research Center of Oncology I.P. Pavlov Ryazan State Medical University
Russian Federation

24, Kashirskoe shosse, 115478-Moscow,Russia

9, Vysokovoltnaya Str., 390026-Ryazan, Russia

PhD, Senior Researcher, Department of Chemical Carcinogenesis, N.N. Blokhin National Medical Research Center of Oncology (Moscow, Russia). Researcher ID (WOS): J-7790-2015. Author ID (Scopus): 583044



References

1. Gupta S.C., Sung B., Prasad S., Webb L.J., Aggarwal B.B. Cancer drug discovery by repurposing: teaching new tricks to old dogs. Trends Pharmacol Sci. 2013 Sep; 34 (9): 508–17. doi: 10.1016/j.tips.2013.06.005.

2. GSM GROUP. Analytical report. Pharmaceutical market in Russia. Results of 2016. 2016; 100. [in Russian]

3. Rotella D.P. Drug discovery 2012 and beyond. ACS Med Chem Lett. 2012 Jan 31; 3 (3): 172–3. doi: 10.1021/ml300022p.

4. Gervas P.A., Litviakov N.V., Popova N.O., Dobrodeev A.Yu., Tarasova A.S., Yumov E.L., Ivanova F.G., Cheremisina O.V., Afanasyev S.G., Goldberg V.E., Cherdyntseva N.V. Problem and perspective to improve molecular testing to choose appropriate target therapy. Siberian Journal of Oncology. 2014; 2: 46–55. [in Russian]

5. Jin G., Wong S.T. Toward better drug repositioning: prioritizing and integrating existing methods into efficient pipelines. Drug Discov Today. 2014 May; 19 (5): 63744. doi: 10.1016/j.drudis.2013.11.005.

6. Pfister D.G. Off-label use of oncology drugs: the need for more data and then some. J Clin Oncol. 2012; 30 (6): 584–6. doi: 10.1200/JCO.2011.38.5567.

7. Swamidass S.J. Mining small-molecule screens to repurpose drugs. Brief Bioinform. 2011 Jul; 12 (4): 327–35. doi: 10.1093/bib/bbr028.

8. Jin G., Fu C., Zhao H., Cui K., Chang J., Wong S.T. A novel method of transcriptional response analysis to facilitate drug repositioning for cancer therapy. Cancer Res. 2012 Jan 1; 72 (1): 33–44. doi: 10.1158/0008-5472.CAN-11-2333.

9. McCabe B., Liberante F., Mills K.I. Repurposing medicinal compounds for blood cancer treatment. Ann Hematol. 2015 Aug; 94 (8): 1267–76. doi: 10.1007/s00277-015-2412-1.

10. Fu C., Jin G., Gao J., Zhu R., Ballesteros-Villagrana E., Wong S.T. DrugMap Central: an on-line query and visualization tool to facilitate drug repositioning studies. Bioinformatics. 2013 Jul 15; 29 (14): 1834–6. doi: 10.1093/bioinformatics/btt279.

11. Zhao H., Jin G., Cui K., Ren D., Liu T., Chen P., Wong S., Li F., Fan Y., Rodriguez A., Chang J., Wong S.T. Novel modeling of cancer cell signaling pathways enables systematic drug repositioning for distinct breast cancer metastases. Cancer Res. 2013 Oct 15; 73 (20): 6149–63. doi: 10.1158/0008-5472.CAN-12-4617.

12. Houghton P.J., Morton C.L., Gorlick R., Lock R.B., Carol H., Reynolds C.P., Kang M.H., Maris J.M., Keir S.T., Kolb E.A., Wu J., Wozniak A.W., Billups C.A., Rubinstein L., Smith M.A. Stage 2 combination testing of rapamycin with cytotoxic agents by the Pediatric Preclinical Testing Program. Mol Cancer Ther. 2010 Jan; 9 (1): 10112. doi: 10.1158/1535-7163.MCT-09-0952.

13. Blatt J. Corey S.J. Drug repurposing in pediatrics and pediatric hematology oncology. Drug Discov Today. 2013 Jan; 18 (1–2): 4–10. doi: 10.1016/j.drudis.2012.07.009.

14. Sirota M., Dudley J.T., Kim J., Chiang A.P., Morgan A.A., Sweet- Cordero A., Sage J., Butte A.J. Discovery and preclinical validation of drug indications using compendia of public gene expression data. SSci Transl Med. 2011 Aug 17; 3 (96): 96ra77. doi: 10.1126/scitranslmed.3001318.

15. Chen X., Yan C.C., Zhang X., Zhang X., Dai F., Yin J., Zhang Y. Drug-target interaction prediction: databases, web servers and computational models. Brief Bioinform. 2016 Jul; 17 (4): 696–712. doi: 10.1093/bib/bbv066.

16. Liu Z., Fang H., Reagan K., Xu X., Mendrick D.L., Slikker W., Jr., Tong W. In silico drug repositioning: what we need to know. Drug Discov Today. 2013 Feb; 18 (3–4): 110–5. doi: 10.1016/j.drudis.2012.08.005.

17. Wu Z., Wang Y., Chen L. Network-based drug repositioning. Mol Biosyst. 2013 Jun; 9 (6): 1268–81. doi: 10.1039/c3mb25382a.

18. Cheng F., Hong H., Yang S., Wei Y. Individualized network-based drug repositioning infrastructure for precision oncology in the panomics era. Brief Bioinform. 2017 Jul 1; 18 (4): 682–697. doi: 10.1093/bib/bbw051.

19. Pritchard J.E., O’Mara T.A., Glubb D.M. Enhancing the Promise of Drug Repositioning through Genetics. Front Pharmacol. 2017 Dec 6; 8: 896. doi: 10.3389/fphar.2017.00896.

20. Lamb J., Crawford E.D., Peck D., Modell J.W., Blat I.C., Wrobel M.J., Lerner J., Brunet J.P., Subramanian A., Ross K.N., Reich M., Hieronymus H., Wei G., Armstrong S.A., Haggarty S.J., Clemons P.A., Wei R., Carr S.A., Lander E.S., Golub T.R. The Connectivity Map: using gene-expression signatures to connect small molecules, genes, and disease. Science. 2006; 313 (5795): 1929–35.

21. Duan Q., Flynn C., Niepel M., Hafner M., Muhlich J.L., Fernandez N.F., Rouillard A.D., Tan C.M., Chen E.Y., Golub T.R., Sorger P.K., Subramanian A., Ma’ayan A. LINCS Canvas Browser: interactive web app to query, browse and interrogate LINCS L1000 gene expression signatures. Nucleic Acids Res. 2014 Jul; 42 (Web Server issue): W449–60. doi: 10.1093/nar/gku476.

22. Korman D. Drug repurposing in oncology. Practical Oncology. 2017; 18 (1): 139–158. [in Russian]

23. Naberezhnov D., Glazunov V., Lesovaya E., Belitsky G., Yakubovskaya M., Kirsanov K. Influence of minor groove binding ligands on PARP1 activation: comparative analysis. Modern Problems of Science and Education. 2016; 6: 134–134. [in Russian]

24. Kirsanov K.I., Kotova E., Makhov P., Golovine K., Lesovaya E.A., Kolenko V.M., Yakubovskaya M.G., Tulin A.V. Minor grove binding ligands disrupt PARP-1 activation pathways. Oncotarget. 2014; 5 (2): 428–37.

25. Zhou J., Le V., Kalia D., Nakayama S., Mikek C., Lewis E.A., Sintim H.O. Diminazene or berenil, a classic duplex minor groove binder, binds to G-quadruplexes with low nanomolar dissociation constants and the amidine groups are also critical for G-quadruplex binding. Mol Biosyst. 2014; 10 (10): 2724–34.

26. Wang C., Carter-Cooper B., Du Y., Zhou J., Saeed M.A., Liu J., Guo M., Roembke B., Mikek C., Lewis E.A., Lapidus R.G., and Sintim H.O. Alkyne-substituted diminazene as G-quadruplex binders with anticancer activities. Eur J Med Chem. 2016 Aug 8; 118: 266–75. doi: 10.1016/j.ejmech.2016.04.030.

27. Gegotek A., Cyunczyk M., Luczaj W., Bielawska A., Bielawski K., Skrzydlewska E. The redox status of human breast cancer cell lines (MCF-7 and MDA-MB231) treated with novel dinuclear berenil-platinum(II) complexes. Pharmazie. 2014; 69 (12): 923–8.

28. Jarocka I., Gegotek A., Bielawska A., Bielawski K., Luczaj W., Hodun T., Skrzydlewska E. Effect of novel dinuclear platinum(II) complexes on redox status of MOLT-4 leukemic cells. Toxicol Mech Methods. 2013 Nov; 23 (9): 641–9. doi: 10.3109/15376516.2013.825359.

29. Bielawski K., Czarnomysy R., Muszynska A., Bielawska A., Poplawska B. Cytotoxicity and induction of apoptosis of human breast cancer cells by novel platinum(II) complexes. Environ Toxicol Pharmacol. 2013 Mar; 35 (2): 254–64. doi: 10.1016/j.etap.2012.12.010.

30. Czarnomysy R., Bielawska A., Muszynska A., Bielawski K. Effects of novel alkyl pyridine platinum complexes on apoptosis in Ishikawa endometrial cancer cells. Med Chem. 2015; 11 (6): 540–50.

31. Gornowicz A., Bielawska A., Szymanowski W., Gabryel-Porowska H., Czarnomysy R., Bielawski K. Mechanism of anticancer action of novel berenil complex of platinum(II) combined with anti-MUC1 in MCF-7 breast cancer cells. Oncol Lett. 2018 Feb; 15 (2): 2340–2348. doi: 10.3892/ol.2017.7623.

32. Lesovaya E., Agarwal S., Readhead B., Vinokour E., Baida G., Bhalla P., Kirsanov K., Yakubovskaya M., Platanias L.C., Dudley J.T., Budunova I. Rapamycin modulates glucocorticoid receptor function, blocks atrophogene REDD1, and protects skin from steroid atrophy. J Invest Dermatol. 2018 Mar 26. pii: S0022-202X(18)31809-8. doi: 10.1016/j.jid.2018.02.045.

33. Baida G., Bhalla P., Kirsanov K., Lesovaya E., Yakubovskaya M., Yuen K., Guo S., Lavker R.M., Readhead B., Dudley J.T., Budunova I. REDD1 functions at the crossroads between the therapeutic and adverse effects of topical glucocorticoids. EMBO Mol Med. 2015 Jan; 7 (1): 42–58. doi: 10.15252/emmm.201404601.

34. Fischkoff S.A., Walter E.Jr. Induction of neutrophilic differentiation of human promyelocytic leukemic cells by branched-chain carboxylic acid anticonvulsant drugs. J Biol Response Mod. 1984; 3 (2): 132–7.

35. Gu S., Tian Y., Chlenski A., Salwen H.R., Lu Z., Raj J.U., Yang Q. Valproic acid shows a potent antitumor effect with alteration of DNA methylation in neuroblastoma. Anticancer Drugs. 2012; 23 (10): 1054–66.

36. Michaelis M., Doerr H.W., Cinatl J.Jr. Valproic acid as anti-cancer drug. Curr Pharm Des. 2007; 13 (33): 3378–93.

37. Leaute-Labreze C., Dumas de la Roque E., Hubiche T., Boralevi F., Thambo J.B., Taieb A. Propranolol for severe hemangiomas of infancy. N Engl J Med. 2008 Jun 12; 358 (24): 2649–51. doi: 10.1056/NEJMc0708819.

38. Zhang L., Mai H.M., Zheng J., Zheng J.W., Wang Y.A., Qin Z.P., and Li K.L. Propranolol inhibits angiogenesis via down-regulating the expression of vascular endothelial growth factor in hemangioma derived stem cell. Int J Clin Exp Pathol. 2014; 7 (1): 48–55.

39. Greenberger S., Bischoff J. Infantile hemangioma-mechanism(s) of drug action on a vascular tumor. Cold Spring Harb Perspect Med. 2011; 1 (1): a006460.

40. Kuang X., Qi M., Peng C., Zhou C., Su J., Zeng W., Liu H., Zhang J., Chen M., Shen M., Xie X., Li F., Zhao S., Li Q., Luo Z., Chen J., Tao J., He Y., Chen X. Propranolol enhanced the anti-tumor effect of sunitinib by inhibiting proliferation and inducing G0/G1/S phase arrest in malignant melanoma. Oncotarget. 2017 Nov 25; 9 (1): 802–811. doi: 10.18632/oncotarget.22696.

41. Montoya A., Amaya C.N., Belmont A., Diab N., Trevino R., Villanueva G., Rains S., Sanchez L.A., Badri N., Otoukesh S., Khammanivong A., Liss D., Baca S.T., Aguilera R.J., Dickerson E.B., Torabi A., Dwivedi A.K., Abbas A., Chambers K., Bryan B.A., Nahleh Z. Use of non-selective beta-blockers is associated with decreased tumor proliferative indices in early stage breast cancer. Oncotarget. 2017 Jan 24; 8 (4): 6446–6460. doi: 10.18632/oncotarget.14119.

42. Wang F., Liu H., Wang F., Xu R., Wang P., Tang F., Zhang X., Zhu Z., Lv H., and Han T. Propranolol suppresses the proliferation and induces the apoptosis of liver cancer cells. Mol Med Rep. 2018 Apr; 17 (4): 5213–5221. doi: 10.3892/mmr.2018.8476.

43. Jang H.I., Lim S.H., Lee Y.Y., Kim T.J., Choi C.H., Lee J.W., Kim B.G., Bae D.S. Perioperative administration of propranolol to women undergoing ovarian cancer surgery: A pilot study. Obstet Gynecol Sci. 2017 Mar; 60 (2): 170–177. doi: 10.5468/ogs.2017.60.2.170.

44. Stenvang J., Kumler I., Nygard S.B., Smith D.H., Nielsen D., Brunner N., Moreira J.M. Biomarker-guided repurposing of chemotherapeutic drugs for cancer therapy: a novel strategy in drug development. Front Oncol. 2013 Dec 25; 3: 313. doi: 10.3389/fonc.2013.00313.

45. Horisberger K., Erben P., Muessle B., Woernle C., Stroebel P., Kaehler G., Wenz F., Hochhaus A., Post S., Willeke F., Hofheinz R.D.; MARGIT (Mannheimer Arbeitsgruppe für Gastrointestinale Tumoren). I expression correlates to response to neoadjuvant irinotecan-based chemoradiation in rectal cancer. Anticancer Drugs. 2009 Jul; 20 (6): 519–24. doi: 10.1097/CAD.0b013e32832b53ff.

46. Lan H., Li Y., Lin C.Y. Irinotecan as a palliative therapy for metastatic breast cancer patients after previous chemotherapy. Asian Pac J Cancer Prev. 2014; 15 (24): 10745–8.

47. Kumler I., Brunner N., Stenvang J., Balslev E., Nielsen D.L. A systematic review on topoisomerase 1 inhibition in the treatment of metastatic breast cancer. Breast Cancer Res Treat. 2013 Apr; 138 (2): 347–58. doi: 10.1007/s10549-013-2476-3.


Review

For citations:


Savinkova A.V., Zhidkova E.M., Tilova L.R., Lavrova M.D., Lylova E.S., Kuzin K.A., Portyannikova A.Yu., Maximova V.P., Kholodova A.V., Vlasova O.A., Fetisov T.I., Kirsanov K.I., Belitskiy G.A., Yakubovskaya M.G., Lesovaya E.A. VARIANTS AND PERSPECTIVES OF DRUG REPURPOSING FOR CANCER TREATMENT. Siberian journal of oncology. 2018;17(3):77-87. (In Russ.) https://doi.org/10.21294/1814-4861-2018-17-3-77-87

Views: 1242


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 1814-4861 (Print)
ISSN 2312-3168 (Online)