Login Register Cart 0
Generic placeholder image

Current Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe Translate in Chinese
Review Article

Drug Repurposing in the Development of Anticancer Agents

Author(s): Sureyya Olgen* and Lakshmi P. Kotra*

Volume 26, Issue 28, 2019

Page: [5410 - 5427] Pages: 18

DOI: 10.2174/0929867325666180713155702

Price: $65

Abstract

Background: Research into repositioning known drugs to treat cancer other than the originally intended disease continues to grow and develop, encouraged in part, by several recent success stories. Many of the studies in this article are geared towards repurposing generic drugs because additional clinical trials are relatively easy to perform and the drug safety profiles have previously been established.

Objective: This review provides an overview of anticancer drug development strategies which is one of the important areas of drug restructuring.

Methods: Repurposed drugs for cancer treatments are classified by their pharmacological effects. The successes and failures of important repurposed drugs as anticancer agents are evaluated in this review.

Results and Conclusion: Drugs could have many off-target effects, and can be intelligently repurposed if the off-target effects can be employed for therapeutic purposes. In cancer, due to the heterogeneity of the disease, often targets are quite diverse, hence a number of already known drugs that interfere with these targets could be deployed or repurposed with appropriate research and development.

Keywords: Drug repurposing, anticancer, drug development, recent applications, clinical trials, off-target effects.

« Previous
[1]
Nosengo, N. New tricks for old drugs. Nature, 2016, 534, 314-316.
[http://dx.doi.org/10.1038/534314a] [PMID: 27306171]
[2]
Ashburn, T.T.; Thor, K.B. Drug repositioning: identifying and developing new uses for existing drugs. Nat. Rev. Drug Discov., 2004, 3(8), 673-683.
[http://dx.doi.org/10.1038/nrd1468] [PMID: 15286734]
[3]
Chen, H.; Wu, J.; Gao, Y.; Chen, H.; Zhou, J. Scaffold repurposing of old drugs towards new cancer drug discovery. Curr. Top. Med. Chem., 2016, 16(19), 2107-2114.
[http://dx.doi.org/10.2174/1568026616666160216155556] [PMID: 26881709]
[4]
Andronis, C.; Sharma, A.; Virvilis, V.; Deftereos, S.; Persidis, A. Literature mining, ontologies and information visualization for drug repurposing. Brief. Bioinform., 2011, 12(4), 357-368.
[http://dx.doi.org/10.1093/bib/bbr005] [PMID: 21712342]
[5]
March-Vila, E.; Pinzi, L.; Sturm, N.; Tinivella, A.; Engkvist, O.; Chen, H.; Rastelli, G. On the Integration of in silico drug design methods for drug repurposing. Front. Pharmacol., 2017, 8, 298-304.
[http://dx.doi.org/10.3389/fphar.2017.00298] [PMID: 28588497]
[6]
Chopra, G.; Samudrala, R. Exploring polypharmacology in drug discovery and repurposing using the CANDO platform. Curr. Pharm. Des., 2016, 22(21), 3109-3123.
[http://dx.doi.org/10.2174/1381612822666160325121943] [PMID: 27013226]
[7]
Reddy, A.S.; Zhang, S. Polypharmacology: Drug discovery for the future. Expert Rev. Clin. Pharmacol., 2013, 6(1), 41-47.
[http://dx.doi.org/10.1586/ecp.12.74] [PMID: 23272792]
[8]
Turner, N.; Zeng, X-Y.; Osborne, B.; Rogers, S.; Ye, J-M. Repurposing drugs to target the diabetes epidemic. Trends Pharmacol. Sci., 2016, 37(5), 379-389.
[http://dx.doi.org/10.1016/j.tips.2016.01.007] [PMID: 26900045]
[9]
Huang, J.; Zhao, D.; Liu, Z.; Liu, F. Repurposing psychiatric drugs as anticancer agents. Cancer Lett., 2018, 419, 257-265.
[http://dx.doi.org/10.1016/j.cancet.2018.01.058] [PMID: 29414306]
[10]
Zhou, S.; Wang, F.; Hsieh, T-C.; Wu, J.M.; Wu, E. Thalidomide-a notorious sedative to a wonder anticancer drug. Curr. Med. Chem., 2013, 20(33), 4102-4108.
[http://dx.doi.org/10.2174/09298673113209990198] [PMID: 23931282]
[11]
Stephens, T.D.; Fillmore, B.J. Hypothesis: thalidomide embryopathy-proposed mechanism of action. Teratology, 2000, 61(3), 189-195.
[http://dx.doi.org/10.1002/(SICI)1096-9926(200003)61:3<189:AID-TERA6>3.0.CO;2-W] [PMID: 10661908]
[12]
Hideshima, T.; Raje, N.; Richardson, P.G.; Anderson, K.C. A review of lenalidomide in combination with dexamethasone for the treatment of multiple myeloma. Ther. Clin. Risk Manag., 2008, 4(1), 129-136.
[http://dx.doi.org/10.2147/TCRM.S1445] [PMID: 18728702]
[13]
Galustian, C.; Dalgleish, A. Lenalidomide: a novel anticancer drug with multiple modalities. Expert Opin. Pharmacother., 2009, 10(1), 125-133.
[http://dx.doi.org/10.1517/14656560802627903] [PMID: 19236186]
[14]
Richardson, P.G.; Weller, E.; Lonial, S.; Jakubowiak, A.J.; Jagannath, S.; Raje, N.S.; Avigan, D.E.; Xie, W.; Ghobrial, I.M.; Schlossman, R.L.; Mazumder, A.; Munshi, N.C.; Vesole, D.H.; Joyce, R.; Kaufman, J.L.; Doss, D.; Warren, D.L.; Lunde, L.E.; Kaster, S.; Delaney, C.; Hideshima, T.; Mitsiades, C.S.; Knight, R.; Esseltine, D-L.; Anderson, K.C. Lenalidomide, bortezomib, and dexamethasone combination therapy in patients with newly diagnosed multiple myeloma. Blood, 2010, 116(5), 679-686.
[http://dx.doi.org/10.1182/blood-2010-02-268862] [PMID: 20385792]
[15]
Licht, J.D.; Shortt, J.; Johnstone, R. From anecdote to targeted therapy: the curious case of thalidomide in multiple myeloma. Cancer Cell, 2014, 25(1), 9-11.
[http://dx.doi.org/10.1016/j.ccr.2013.12.019] [PMID: 24434206]
[16]
Ríos-Tamayo, R.; Martín-García, A.; Alarcón-Payer, C.; Sánchez-Rodríguez, D.; de la Guardia, A.M.D.V.D.; García Collado, C.G.; Jiménez Morales, A.; Jurado Chacón, M.; Cabeza Barrera, J. Pomalidomide in the treatment of multiple myeloma: design, development and place in therapy. Drug Des. Devel. Ther., 2017, 11, 2399-2408.
[http://dx.doi.org/10.2147/DDDT.S115456] [PMID: 28860711]
[17]
Agarwala, S.S.; Kirkwood, J.M. Temozolomide, a novel alkylating agent with activity in the central nervous system, may improve the treatment of advanced metastatic melanoma. Oncologist, 2000, 5(2), 144-151.
[http://dx.doi.org/10.1634/theoncologist.5-2-144] [PMID: 10794805]
[18]
Hwu, W.J. New approaches in the treatment of metastatic melanoma: Thalidomide and temozolomide. Oncology (Williston Park), 2000, 14(12)(Suppl. 13), 25-28.
[PMID: 11204670]
[19]
Soape, M.P.; Verma, R.; Payne, J.D.; Wachtel, M.; Hardwicke, F.; Cobos, E. Treatment of Hepatic epithelioid hemangioendothelioma: finding uses for thalidomide in a new era of medicine. Case Rep. Gastrointest. Med., 2015, 2015326795
[20]
Eisen, T.; Boshoff, C.; Mak, I.; Sapunar, F.; Vaughan, M.M.; Pyle, L.; Johnston, S.R.D.; Ahern, R.; Smith, I.E.; Gore, M.E. Continuous low dose Thalidomide: A phase II study in advanced melanoma, renal cell, ovarian and breast cancer. Br. J. Cancer, 2000, 82(4), 812-817.
[http://dx.doi.org/10.1054/bjoc.1999.1004] [PMID: 10732751]
[21]
Hwang, C.; Heath, E.I. Angiogenesis inhibitors in the treatment of prostate cancer. J. Hematol. Oncol., 2010, 3(26), 26.
[http://dx.doi.org/10.1186/1756-8722-3-26] [PMID: 20678204]
[22]
Keifer, J.A.; Guttridge, D.C.; Ashburner, B.P.; Baldwin, A.S. Jr Inhibition of NF-kappa B activity by thalidomide through suppression of IkappaB kinase activity. J. Biol. Chem., 2001, 276(25), 22382-22387.
[http://dx.doi.org/10.1074/jbc.M100938200] [PMID: 11297551]
[23]
Gasic, G.J.; Gasic, T.B.; Murphy, S. Anti-metastatic effect of aspirin. Lancet, 1972, 2(7783), 932-933.
[http://dx.doi.org/10.1016/S0140-6736(72)92581-0] [PMID: 4116642]
[24]
Rothwell, P.M.; Fowkes, F.G.; Belch, J.F.; Ogawa, H.; Warlow, C.P.; Meade, T.W. Effect of daily aspirin on long-term risk of death due to cancer: analysis of individual patient data from randomised trials. Lancet, 2011, 377(9759), 31-41.
[http://dx.doi.org/10.1016/S0140-6736(10)62110-1] [PMID: 21144578]
[25]
Din, F.V.; Theodoratou, E.; Farrington, S.M.; Tenesa, A.; Barnetson, R.A.; Cetnarskyj, R.; Stark, L.; Porteous, M.E.; Campbell, H.; Dunlop, M.G. Effect of aspirin and NSAIDs on risk and survival from colorectal cancer. Gut, 2010, 59(12), 1670-1679.
[http://dx.doi.org/10.1136/gut.2009.203000] [PMID: 20844293]
[26]
Turini, M.E.; DuBois, R.N. Cyclooxygenase-2: A therapeutic target. Annu. Rev. Med., 2002, 53, 35-57.
[http://dx.doi.org/10.1146/annurev.med.53.082901.103952] [PMID: 11818462]
[27]
Sobolewski, C.; Cerella, C.; Dicato, M.; Ghibelli, L.; Diederich, M. The role of cyclooxygenase-2 in cell proliferation and cell death in human malignancies. Int. J. Cell Biol., 2010, 2010215158
[http://dx.doi.org/10.1155/2010/215158]
[28]
Lanas, A. Clinical experience with cyclooxygenase-2 inhibitors. Rheumatology (Oxford), 2002, 41(Suppl. 1), 16-22.
[http://dx.doi.org/10.1093/rheumatology/41.S1.16] [PMID: 12173276]
[29]
FitzGerald, G.A.; Patrono, C. The coxibs, selective inhibitors of cyclooxygenase-2. N. Engl. J. Med., 2001, 345(6), 433-442.
[http://dx.doi.org/10.1056/NEJM200108093450607] [PMID: 11496855]
[30]
Jendrossek, V. Targeting apoptosis pathways by celecoxib in cancer. Cancer Lett., 2013, 332(2), 313-324.
[http://dx.doi.org/10.1016/j.canlet.2011.01.012] [PMID: 21345578]
[31]
Steinbach, G.; Lynch, P.M.; Phillips, R.K.; Wallace, M.H.; Hawk, E.; Gordon, G.B.; Wakabayashi, N.; Saunders, B.; Shen, Y.; Fujimura, T.; Su, L.K.; Levin, B.; Godio, L.; Patterson, S.; Rodriguez-Bigas, M.A.; Jester, S.L.; King, K.L.; Schumacher, M.; Abbruzzese, J.; DuBois, R.N.; Hittelman, W.N.; Zimmerman, S.; Sherman, J.W.; Kelloff, G. The effect of celecoxib, a cyclooxygenase-2 inhibitor, in familial adenomatous polyposis. N. Engl. J. Med., 2000, 342(26), 1946-1952.
[http://dx.doi.org/10.1056/NEJM200006293422603] [PMID: 10874062]
[32]
Schönthal, A.H. Direct non-cyclooxygenase-2 targets of celecoxib and their potential relevance for cancer therapy. Br. J. Cancer, 2007, 97(11), 1465-1468.
[http://dx.doi.org/10.1038/sj.bjc.6604049] [PMID: 17955049]
[33]
Harris, R.E. Cyclooxygenase-2 (cox-2) blockade in the chemoprevention of cancers of the colon, breast, prostate, and lung. Inflammopharmacology, 2009, 17(2), 55-67.
[http://dx.doi.org/10.1007/s10787-009-8049-8] [PMID: 19340409]
[34]
Friedman, G.D.; Ury, H.K. Initial screening for carcinogenicity of commonly used drugs. J. Natl. Cancer Inst., 1980, 65(4), 723-733.
[http://dx.doi.org/10.1093/jnci/65.4.723] [PMID: 6932525]
[35]
Harris, R.E.; Beebe-Donk, J.; Alshafie, G.A. Reduction in the risk of human breast cancer by selective cyclooxygenase-2 (COX-2) inhibitors. BMC Cancer, 2006, 6, 27.
[http://dx.doi.org/10.1186/1471-2407-6-27] [PMID: 16445867]
[36]
Algra, A.M.; Rothwell, P.M. Effects of regular aspirin on long-term cancer incidence and metastasis: a systematic comparison of evidence from observational studies versus randomised trials. Lancet Oncol., 2012, 13(5), 518-527.
[http://dx.doi.org/10.1016/S1470-2045(12)70112-2] [PMID: 22440112]
[37]
Gong, L.; Thorn, C.F.; Bertagnolli, M.M.; Grosser, T.; Altman, R.B.; Klein, T.E. Celecoxib pathways: Pharmacokinetics and pharmacodynamics. Pharmacogenet. Genomics, 2012, 22(4), 310-318.
[http://dx.doi.org/10.1097/FPC.0b013e32834f94cb] [PMID: 22336956]
[38]
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, 34(9), 508-517.
[http://dx.doi.org/10.1016/j.tips.2013.06.005] [PMID: 23928289]
[39]
Regulski, M.; Regulska, K.; Prukała, W.; Piotrowska, H.; Stanisz, B.; Murias, M. COX-2 inhibitors: A novel strategy in the management of breast cancer. Drug Discov. Today, 2016, 21(4), 598-615.
[http://dx.doi.org/10.1016/j.drudis.2015.12.003] [PMID: 26723915]
[40]
Falandry, C.; Debled, M.; Bachelot, T.; Delozier, T.; Crétin, J.; Romestaing, P.; Mille, D.; You, B.; Mauriac, L.; Pujade-Lauraine, E.; Freyer, G. Celecoxib and exemestane versus placebo and exemestane in postmenopausal metastatic breast cancer patients: A double-blind phase III GINECO study. Breast Cancer Res. Treat., 2009, 116(3), 501-508.
[http://dx.doi.org/10.1007/s10549-008-0229-5] [PMID: 19020973]
[41]
Chateauvieux, S.; Morceau, F.; Dicato, M.; Marc Diederich, M. Molecular and therapeutic potential and toxicity of valproic acid. J. Biomed. Biotechnol., 2010.479364
[http://dx.doi.org/10.1155/2010/479364]
[42]
Kostrouchová, M.; Kostrouch, Z.; Kostrouchová, M. Valproic acid, a molecular lead to multiple regulatory pathways. Folia Biol. (Praha), 2007, 53(2), 37-49.
[PMID: 17448293]
[43]
Blaheta, R.A.; Michaelis, M.; Driever, P.H.; Cinatl, J., Jr Evolving anticancer drug valproic acid: Insights into the mechanism and clinical studies. Med. Res. Rev., 2005, 25(4), 383-397.
[http://dx.doi.org/10.1002/med.20027] [PMID: 15637697]
[44]
Raffoux, E.; Chaibi, P.; Dombret, H.; Degos, L. Valproic acid and all-trans retinoic acid for the treatment of elderly patients with acute myeloid leukemia. Haematologica, 2005, 90(7), 986-988.
[PMID: 15996941]
[45]
Michaelis, M.; Doerr, H.W.; Cinatl, J., Jr Valproic acid as anti-cancer drug. Curr. Pharm. Des., 2007, 13(33), 3378-3393.
[http://dx.doi.org/10.2174/138161207782360528] [PMID: 18045192]
[46]
Abdul, M.; Hoosein, N. Inhibition by anticonvulsants of prostate-specific antigen and interleukin-6 secretion by human prostate cancer cells. Anticancer Res., 2001, 21(3B), 2045-2048.
[PMID: 11497296]
[47]
Krämer, O.H.; Baus, D.; Knauer, S.K.; Stein, S.; Jäger, E.; Stauber, R.H.; Grez, M.; Pfitzner, E.; Heinzel, T. Acetylation of Stat1 modulates NF-kappaB activity. Genes Dev., 2006, 20(4), 473-485.
[http://dx.doi.org/10.1101/gad.364306] [PMID: 16481475]
[48]
Ziauddin, M.F.; Yeow, W-S.; Maxhimer, J.B.; Baras, A.; Chua, A.; Reddy, R.M.; Tsai, W.; Cole, G.W., Jr; Schrump, D.S.; Nguyen, D.M. Valproic acid, an antiepileptic drug with histone deacetylase inhibitory activity, potentiates the cytotoxic effect of Apo2L/TRAIL on cultured thoracic cancer cells through mitochondria-dependent caspase activation. Neoplasia, 2006, 8(6), 446-457.
[http://dx.doi.org/10.1593/neo.05823] [PMID: 16820090]
[49]
Venkataramani, V.; Rossner, C.; Iffland, L.; Schweyer, S.; Tamboli, I.Y.; Walter, J.; Wirths, O.; Bayer, T.A. Histone deacetylase inhibitor valproic acid inhibits cancer cell proliferation via down-regulation of the alzheimer amyloid precursor protein. J. Biol. Chem., 2010, 285(14), 10678-10689.
[http://dx.doi.org/10.1074/jbc.M109.057836] [PMID: 20145244]
[50]
Nelson, M.; Yang, M.; Dowle, A.A.; Thomas, J.R.; Brackenbury, W.J. The sodium channel-blocking antiepileptic drug phenytoin inhibits breast tumour growth and metastasis. Mol. Cancer, 2015, 14(13), 13.
[http://dx.doi.org/10.1186/s12943-014-0277-x] [PMID: 25623198]
[51]
Pellegrino, M.; Rizza, P.; Nigro, A.; Ceraldi, R.; Ricci, E.; Perrotta, I.; Aquila, S.; Lanzino, M.; Andò, S.; Morelli, C.; Sisci, D. FoxO3a mediates the inhibitory effects of the antiepileptic drug lamotrigine on breast cancer growth. Mol. Cancer Res., 2018, 16(6), 923-934.
[http://dx.doi.org/10.1158/1541-7786.MCR-17-0662] [PMID: 29523760]
[52]
Papanagnou, P.; Stivarou, T.; Papageorgiou, I.; Papadopoulos, G.E.; Pappas, A. Marketed drugs used for the management of hypercholesterolemia as anticancer armament. OncoTargets Ther., 2017, 10, 4393-4411.
[http://dx.doi.org/10.2147/OTT.S140483] [PMID: 28932124]
[53]
Burke, L.P.; Kukoly, C.A. Statins induce lethal effects in acute myeloblastic leukemia cells within 72 hours. Leuk. Lymphoma, 2008, 49(2), 322-330.
[http://dx.doi.org/10.1080/10428190701760011] [PMID: 18231920]
[54]
Chae, Y.K.; Yousaf, M.; Malecek, M-K.; Carneiro, B.; Chandra, S.; Kaplan, J.; Kalyan, J.; Sassano, A.; Platanias, L.C.; Giles, F. 2015.http://www.discoverymedicine.com
[55]
Crosbie, J.; Magnussen, M.; Dornbier, R.; Iannone, A.; Steele, T.A. Statins inhibit proliferation and cytotoxicity of a human leukemic natural killer cell line. Biomark. Res., 2013, 1(1), 33.
[http://dx.doi.org/10.1186/2050-7771-1-33] [PMID: 24359683]
[56]
Ahn, K.S.; Sethi, G.; Aggarwal, B.B. Simvastatin potentiates TNF-alpha-induced apoptosis through the down-regulation of NF-kappaB-dependent antiapoptotic gene products: role of IkappaBalpha kinase and TGF-beta-activated kinase-1. J. Immunol., 2007, 178(4), 2507-2516.
[http://dx.doi.org/10.4049/jimmunol.178.4.2507] [PMID: 17277159]
[57]
Broughton, T.; Sington, J.; Beales, I.L.P. Statin use is associated with a reduced incidence of colorectal cancer: a colonoscopy-controlled case-control study. BMC Gastroenterol., 2012, 12, 36.
[http://dx.doi.org/10.1186/1471-230X-12-36] [PMID: 22530742]
[58]
Coogan, P.F.; Smith, J.; Rosenberg, L. Statin use and risk of colorectal cancer. J. Natl. Cancer Inst., 2007, 99(1), 32-40.
[http://dx.doi.org/10.1093/jnci/djk003] [PMID: 17202111]
[59]
Shadman, M.; Mawad, R.; Dean, C.; Chen, T.L.; Shannon-Dorcy, K.; Sandhu, V.; Hendrie, P.C.; Scott, B.L.; Walter, R.B.; Becker, P.S.; Pagel, J.M.; Estey, E.H. Idarubicin, cytarabine, and pravastatin as induction therapy for untreated acute myeloid leukemia and high-risk myelodysplastic syndrome. Am. J. Hematol., 2015, 90(6), 483-486.
[http://dx.doi.org/10.1002/ajh.23981] [PMID: 25689471]
[60]
Pradelli, D.; Soranna, D.; Zambon, A.; Catapano, A.; Mancia, G.; La Vecchia, C.; Corrao, G. Statins use and the risk of all and subtype hematological malignancies: A meta-analysis of observational studies. Cancer Med., 2015, 4(5), 770-780.
[http://dx.doi.org/10.1002/cam4.411] [PMID: 25809667]
[61]
Altwairgi, A.K. Statins are potential anticancerous agents (review). Oncol. Rep., 2015, 33(3), 1019-1039.
[http://dx.doi.org/10.3892/or.2015.3741] [PMID: 25607255]
[62]
Kalender, A.; Selvaraj, A.; Kim, S.Y.; Gulati, P.; Brûlé, S.; Viollet, B.; Kemp, B.E.; Bardeesy, N.; Dennis, P.; Schlager, J.J.; Marette, A.; Kozma, S.C.; Thomas, G. Metformin, independent of AMPK, inhibits mTORC1 in a rag GTPase-dependent manner. Cell Metab., 2010, 11(5), 390-401.
[http://dx.doi.org/10.1016/j.cmet.2010.03.014] [PMID: 20444419]
[63]
Kasznicki, J.; Sliwinska, A.; Drzewoski, J. Metformin in cancer prevention and therapy. Ann. Transl. Med., 2014, 2(6), 57.
[PMID: 25333032]
[64]
Heckman-Stoddard, B.M.; DeCensi, A.; Sahasrabuddhe, V.V.; Ford, L.G. Repurposing metformin for the prevention of cancer and cancer recurrence. Diabetologia, 2017, 60(9), 1639-1647.
[http://dx.doi.org/10.1007/s00125-017-4372-6] [PMID: 28776080]
[65]
Bo, S.; Benso, A.; Durazzo, M.; Ghigo, E. Metformin blocks progression of obesity-activated thyroid cancer in a mouse model. J. Endocrinol. Invest., 2012, 35(2), 231-235.
[http://dx.doi.org/10.1007/BF03345423] [PMID: 22490993]
[66]
Bodmer, M.; Meier, C.; Krähenbühl, S.; Jick, S.S.; Meier, C.R. Long-term metformin use is associated with decreased risk of breast cancer. Diabetes Care, 2010, 33(6), 1304-1308.
[http://dx.doi.org/10.2337/dc09-1791] [PMID: 20299480]
[67]
Jiralerspong, S.; Palla, S.L.; Giordano, S.H.; Meric-Bernstam, F.; Liedtke, C.; Barnett, C.M.; Hsu, L.; Hung, M.C.; Hortobagyi, G.N.; Gonzalez-Angulo, A.M. Metformin and pathologic complete responses to neoadjuvant chemotherapy in diabetic patients with breast cancer. J. Clin. Oncol., 2009, 27(20), 3297-3302.
[http://dx.doi.org/10.1200/JCO.2009.19.6410] [PMID: 19487376]
[68]
Campagnoli, C.; Pasanisi, P.; Abbà, C.; Ambroggio, S.; Biglia, N.; Brucato, T.; Colombero, R.; Danese, S.; Donadio, M.; Venturelli, E.; Zito, G.; Berrino, F. Effect of different doses of metformin on serum testosterone and insulin in non-diabetic women with breast cancer: a randomized study. Clin. Breast Cancer, 2012, 12(3), 175-182.
[http://dx.doi.org/10.1016/j.clbc.2012.03.004] [PMID: 22607767]
[69]
Hosono, K.; Endo, H.; Takahashi, H.; Sugiyama, M.; Sakai, E.; Uchiyama, T.; Suzuki, K.; Iida, H.; Sakamoto, Y.; Yoneda, K.; Koide, T.; Tokoro, C.; Abe, Y.; Inamori, M.; Nakagama, H.; Nakajima, A. Metformin suppresses colorectal aberrant crypt foci in a short-term clinical trial. Cancer Prev. Res. (Phila.), 2010, 3(9), 1077-1083.
[http://dx.doi.org/10.1158/1940-6207.CAPR-10-0186] [PMID: 20810669]
[70]
Zhou, X-L.; Xue, W-H.; Ding, X-F.; Li, L-F.; Dou, M-M.; Zhang, W-J.; Lv, Z.; Fan, Z-R.; Zhao, J.; Wang, L-X. Association between metformin and the risk of gastric cancer in patients with type 2 diabetes mellitus: A meta-analysis of cohort studies. Oncotarget, 2017, 8(33), 55622-55631.
[http://dx.doi.org/10.18632/oncotarget.16973] [PMID: 28903449]
[71]
Tseng, C-H. Metformin reduces gastric cancer risk in patients with type 2 diabetes mellitus. Aging (Albany NY), 2016, 8(8), 1636-1649.
[http://dx.doi.org/10.18632/aging.101019] [PMID: 27587088]
[72]
Li, P.; Zhang, C.; Gao, P.; Chen, X.; Ma, B.; Yu, D.; Song, Y.; Wang, Z. Metformin use and its effect on gastric cancer in patients with type 2 diabetes: A systematic review of observational studies. Oncol. Lett., 2018, 15(1), 1191-1199.
[PMID: 29391902]
[73]
Park, J.; Kim, W.G.; Zhao, L.; Enomoto, K.; Willingham, M.; Cheng, S.Y. Metformin blocks progression of obesity-activated thyroid cancer in a mouse model. Oncotarget, 2016, 7(23), 34832-34844.
[http://dx.doi.org/10.18632/oncotarget.8989] [PMID: 27145454]
[74]
Quinn, B.J.; Kitagawa, H.; Memmott, R.M.; Gills, J.J.; Dennis, P.A. Repositioning metformin for cancer prevention and treatment. Trends Endocrinol. Metab., 2013, 24(9), 469-480.
[http://dx.doi.org/10.1016/j.tem.2013.05.004] [PMID: 23773243]
[75]
Higginbotham, S.; Wong, W.R.; Linington, R.G.; Spadafora, C.; Iturrado, L.; Arnold, A.E. Sloth hair as a novel source of fungi with potent anti-parasitic, anti-cancer and anti-bacterial bioactivity. PLoS One, 2014, 9(1)e84549
[http://dx.doi.org/10.1371/journal.pone.0084549] [PMID: 24454729]
[76]
Johnston, W.T.; Mutalima, N.; Sun, D.; Emmanuel, B.; Bhatia, K.; Aka, P.; Wu, X.; Borgstein, E.; Liomba, G.N.; Kamiza, S.; Mkandawire, N.; Batumba, M.; Carpenter, L.M.; Jaffe, H.; Molyneux, E.M.; Goedert, J.J.; Soppet, D.; Newton, R.; Mbulaiteye, S.M. Relationship between Plasmodium falciparum malaria prevalence, genetic diversity and endemic Burkitt lymphoma in Malawi. Sci. Rep., 2014, 4, 3741.
[http://dx.doi.org/10.1038/srep03741] [PMID: 24434689]
[77]
Khan, K.H. DNA vaccines: Roles against diseases. Germs, 2013, 3(1), 26-35.
[http://dx.doi.org/10.11599/germs.2013.1034] [PMID: 24432284]
[78]
Fedosov, D.A.; Dao, M.; Karniadakis, G.E.; Suresh, S. Computational biorheology of human blood flow in health and disease. Ann. Biomed. Eng., 2014, 42(2), 368-387.
[http://dx.doi.org/10.1007/s10439-013-0922-3] [PMID: 24419829]
[79]
Hooft van Huijsduijnen, R.; Guy, R.K.; Chibale, K.; Haynes, R.K.; Peitz, I.; Kelter, G.; Phillips, M.A.; Vennerstrom, J.L.; Yuthavong, Y.; Wells, T.N. Anticancer properties of distinct antimalarial drug classes. PLoS One, 2013, 8(12)e82962
[http://dx.doi.org/10.1371/journal.pone.0082962] [PMID: 24391728]
[80]
Keum, K.-C.; Yoo, N.-C.; Yoo, W.-M.; Chang, K.K.; Choon, Y.N.; Min, Y.W. Anticancer composition composed of anticancer and anti-malarial drug. WO, 2002.
[81]
Liu, F.; Shang, Y.; Chen, S-Z. Chloroquine potentiates the anti-cancer effect of lidamycin on non-small cell lung cancer cells in vitro. Acta Pharmacol. Sin., 2014, 35(5), 645-652.
[http://dx.doi.org/10.1038/aps.2014.3] [PMID: 24727941]
[82]
Kamal, A.; Aziz, A.; Shouman, S.; El-Demerdash, E.; Elgendy, M.; Abdel-Naim, A.B. Chloroquine as a promising adjuvant chemothreaphy together with sunitinib. Sci. Proc, 2014, 1e384
[83]
Ganguli, A.; Choudhury, D.; Datta, S.; Bhattacharya, S.; Chakrabarti, G. Inhibition of autophagy by chloroquine potentiates synergistically anti-cancer property of artemisinin by promoting ROS dependent apoptosis. Biochimie, 2014, 107(Pt B), 338-349.
[http://dx.doi.org/ 10.1016/j.biochi.2014.10.001] [PMID: 25308836]
[84]
Soo, G.W.; Law, J.H.; Kan, E.; Tan, S.Y.; Lim, W.Y.; Chay, G.; Bukhari, N.I.; Segarra, I. Differential effects of ketoconazole and primaquine on the pharmacokinetics and tissue distribution of imatinib in mice. Anticancer Drugs, 2010, 21(7), 695-703.
[PMID: 20629201]
[85]
Wong, Y.K.; Xu, C.; Kalesh, K.A.; He, Y.; Lin, Q.; Wong, W.S.F.; Shen, H.M.; Wang, J. Artemisinin as an anticancer drug: Recent advances in target profiling and mechanisms of action. Med. Res. Rev., 2017, 37(6), 1492-1517.
[http://dx.doi.org/10.1002/med.21446] [PMID: 28643446]
[86]
Efferth, T. From ancient herb to modern drug: Artemisia annua and artemisinin for cancer therapy. Semin. Cancer Biol., 2017, 46, 65-83.
[http://dx.doi.org/10.1016/j.semcancer.2017.02.009] [PMID: 28254675]
[87]
Olliaro, P.L.; Haynes, R.K.; Meunier, B.; Yuthavong, Y. Possible modes of action of the artemisinin-type compounds. Trends Parasitol., 2001, 17(3), 122-126.
[http://dx.doi.org/10.1016/S1471-4922(00)01838-9] [PMID: 11286794]
[88]
Zhang, S.; Gerhard, G.S. Heme mediates cytotoxicity from artemisinin and serves as a general anti-proliferation target. PLoS One, 2009, 4(10)e7472
[http://dx.doi.org/10.1371/journal.pone.0007472] [PMID: 19862332]
[89]
Hamacher-Brady, A.; Stein, H.A.; Turschner, S.; Toegel, I.; Mora, R.; Jennewein, N.; Efferth, T.; Eils, R.; Brady, N.R. Artesunate activates mitochondrial apoptosis in breast cancer cells via iron-catalyzed lysosomal reactive oxygen species production. J. Biol. Chem., 2011, 286(8), 6587-6601.
[http://dx.doi.org/10.1074/jbc.M110.210047] [PMID: 21149439]
[90]
Das, A.K. Anticancer effect of antimalarial artemisinin compounds. Ann. Med. Health Sci. Res., 2015, 5(2), 93-102.
[http://dx.doi.org/10.4103/2141-9248.153609] [PMID: 25861527]
[91]
Mercer, A.E.; Maggs, J.L.; Sun, X.M.; Cohen, G.M.; Chadwick, J.; O’Neill, P.M.; Park, B.K. Evidence for the involvement of carbon-centered radicals in the induction of apoptotic cell death by artemisinin compounds. J. Biol. Chem., 2007, 282(13), 9372-9382.
[http://dx.doi.org/10.1074/jbc.M610375200] [PMID: 17227762]
[92]
Mercer, A.E.; Copple, I.M.; Maggs, J.L.; O’Neill, P.M.; Park, B.K. The role of heme and the mitochondrion in the chemical and molecular mechanisms of mammalian cell death induced by the artemisinin antimalarials. J. Biol. Chem., 2011, 286(2), 987-996.
[http://dx.doi.org/10.1074/jbc.M110.144188] [PMID: 21059641]
[93]
Bostwick, D.G.; Alexander, E.E.; Singh, R.; Shan, A.; Qian, J.; Santella, R.M.; Oberley, L.W.; Yan, T.; Zhong, W.; Jiang, X.; Oberley, T.D. Antioxidant enzyme expression and reactive oxygen species damage in prostatic intraepithelial neoplasia and cancer. Cancer, 2000, 89(1), 123-134.
[http://dx.doi.org/10.1002/1097-0142(20000701)89:1<123:AID-CNCR17>3.0.CO;2-9] [PMID: 10897009]
[94]
Lu, J.J.; Chen, S.M.; Zhang, X.W.; Ding, J.; Meng, L.H. The anti-cancer activity of dihydroartemisinin is associated with induction of iron-dependent endoplasmic reticulum stress in colorectal carcinoma HCT116 cells. Invest. New Drugs, 2011, 29(6), 1276-1283.
[http://dx.doi.org/10.1007/s10637-010-9481-8] [PMID: 20607588]
[95]
Anfosso, L.; Efferth, T.; Albini, A.; Pfeffer, U. Microarray expression profiles of angiogenesis-related genes predict tumor cell response to artemisinins. Pharmacogenomics J., 2006, 6(4), 269-278.
[http://dx.doi.org/10.1038/sj.tpj.6500371] [PMID: 16432535]
[96]
Nqoro, X.; Tobeka, N.; Aderibigbe, B.A. Quinoline-based hybrid compounds with antimalarial activity. Molecules, 2017, 22(12), 2268-2290.
[http://dx.doi.org/10.3390/molecules22122268] [PMID: 29257067]
[97]
Lu, Y.Y.; Chen, T.S.; Qu, J.L.; Pan, W.L.; Sun, L.; Wei, X.B. Dihydroartemisinin (DHA) induces caspase-3-dependent apoptosis in human lung adenocarcinoma ASTC-a-1 cells. J. Biomed. Sci., 2009, 16, 16.
[http://dx.doi.org/10.1186/1423-0127-16-16] [PMID: 19272183]
[98]
Zhou, C.; Pan, W.; Wang, X.P.; Chen, T.S. Artesunate induces apoptosis via a Bak-mediated caspase-independent intrinsic pathway in human lung adenocarcinoma cells. J. Cell. Physiol., 2012, 227(12), 3778-3786.
[http://dx.doi.org/10.1002/jcp.24086] [PMID: 22378505]
[99]
Efferth, T.; Sauerbrey, A.; Olbrich, A.; Gebhart, E.; Rauch, P.; Weber, H.O.; Hengstler, J.G.; Halatsch, M.E.; Volm, M.; Tew, K.D.; Ross, D.D.; Funk, J.O. Molecular modes of action of artesunate in tumor cell lines. Mol. Pharmacol., 2003, 64(2), 382-394.
[http://dx.doi.org/10.1124/mol.64.2.382] [PMID: 12869643]
[100]
Augustin, Y.; Krishna, S.; Kumar, D.; Pantziarka, P. The wisdom of crowds and the repurposing of artesunate as an anticancer drug. Ecancer. Ecancermedicalscience, 2015, 9ed50
[http://dx.doi.org/10.3332/ecancer.2015.ed50.]
[101]
Džimbeg, G.; Zorc, B.; Kralj, M.; Ester, K.; Pavelić, K.; Andrei, G.; Snoeck, R.; Balzarini, J.; De Clercq, E.; Mintas, M. The novel primaquine derivatives of N-alkyl, cycloalkyl or aryl urea: Synthesis, cytostatic and antiviral activity evaluations. Eur. J. Med. Chem., 2008, 43(6), 1180-1187.
[http://dx.doi.org/10.1016/j.ejmech.2007.09.001] [PMID: 17961851]
[102]
Simunović, M.; Perković, I.; Zorc, B.; Ester, K.; Kralj, M.; Hadjipavlou-Litina, D.; Pontiki, E. Urea and carbamate derivatives of primaquine: synthesis, cytostatic and antioxidant activities. Bioorg. Med. Chem., 2009, 17(15), 5605-5613.
[http://dx.doi.org/10.1016/j.bmc.2009.06.030] [PMID: 19581098]
[103]
Perković, I.; Tršinar, S.; Žanetić, J.; Kralj, M.; Martin-Kleiner, I.; Balzarini, J.; Hadjipavlou-Litina, D.A.M.; Katsori, B.; Zorc, B. Novel 1-acyl-4-substituted semicarbazide derivativesof primaquine-synthesis, cytostatic, antiviral and antioxidative studies. J. Enzyme Inhib. Med. Chem., 2013, 28, 601-610.
[http://dx.doi.org/10.3109/14756366.2012.663366] [PMID: 22380782]
[104]
Pavić, K.; Perković, I.; Cindrić, M.; Pranjić, M.; Martin-Kleiner, I.; Kralj, M.; Schols, D.; Hadjipavlou-Litina, D.; Katsori, A-M.; Zorc, B. Synthesis, biological evaluation, and quantitative structure-activity relationship analysis of new schiff bases of hydroxysemicarbazide as potential antitumor agents. Eur. J. Med. Chem., 2014, 86, 502-514.
[PMID: 25203780]
[105]
Perković, I.; Antunović, M.; Marijanović, I.; Pavić, K.; Ester, K.; Kralj, M.; Vlainić, J.; Kosalec, I.; Schols, D.; Hadjipavlou-Litina, D.; Pontiki, E.; Zorc, B. Novel urea and bis-urea primaquine derivatives with hydroxyphenyl or halogenphenyl substituents: Synthesis and biological evaluation. Eur. J. Med. Chem., 2016, 124, 622-636.
[http://dx.doi.org/10.1016/j.ejmech.2016.08.021] [PMID: 27614409]
[106]
Pavić, K.; Perković, I.; Gilja, P.; Kozlina, F.; Ester, K.; Kralj, M.; Schols, D.; Hadjipavlou-Litina, D.; Pontiki, E.; Zorc, B. Design, synthesis and biological evaluation of novel primaquine-cinnamic acid conjugates of the amide and acylsemicarbazide type. Molecules, 2016, 21(12), 1629-1653.
[http://dx.doi.org/10.3390/molecules21121629] [PMID: 27916811]
[107]
Pavić, K.; Perković, I.; Pospíšilová, Š.; Machado, M.; Fontinha, D.; Prudêncio, M.; Jampilek, J.; Coffey, A.; Endersen, L.; Rimac, H.; Zorc, B. Primaquine hybrids as promising antimycobacterial and antimalarial agents. Eur. J. Med. Chem., 2018, 143, 769-779.
[http://dx.doi.org/10.1016/j.ejmech.2017.11.083] [PMID: 29220797]
[108]
Xu, X.; Wang, J.; Han, K.; Li, S.; Xu, F.; Yang, Y. Antimalarial drug mefloquine inhibits nuclear factor kappa B signaling and induces apoptosis in colorectal cancer cells. Cancer Sci., 2018, 109(4), 1220-1229.
[http://dx.doi.org/10.1111/cas.13540] [PMID: 29453896]
[109]
Verbaanderd, C.; Maes, H.; Schaaf, M.B.; Sukhatme, V.P.; Pantziarka, P.; Sukhatme, V.; Agostinis, P.; Bouche, G. Repurposing Drugs in Oncology (ReDO)-chloroquine and hydroxychloroquine as anti-cancer agents. Ecancermedicalscience, 2017, 11, 781.
[http://dx.doi.org/10.3332/ecancer.2017.781] [PMID: 29225688]
[110]
Shaimerdenova, M.; Karapina, O.; Mektepbayeva, D.; Alibek, K.; Akilbekova, D. The effects of antiviral treatment on breast cancer cell line. Infect. Agent. Cancer, 2017, 12, 18.
[http://dx.doi.org/10.1186/s13027-017-0128-7] [PMID: 28344640]
[111]
Monini, P.; Sgadari, C.; Toschi, E.; Barillari, G.; Ensoli, B. Antitumour effects of antiretroviral therapy. Nat. Rev. Cancer, 2004, 4(11), 861-875.
[http://dx.doi.org/10.1038/nrc1479] [PMID: 15516959]
[112]
Mitsuya, H.; Weinhold, K.J.; Furman, P.A.; St Clair, M.H.; Lehrman, S.N.; Gallo, R.C.; Bolognesi, D.; Barry, D.W.; Broder, S. 3′-Azido-3′-deoxythymidine (BW A509U): an antiviral agent that inhibits the infectivity and cytopathic effect of human T-lymphotropic virus type III/lymphadenopathy-associated virus in vitro. Proc. Natl. Acad. Sci. USA, 1985, 82(20), 7096-7100.
[http://dx.doi.org/10.1073/pnas.82.20.7096] [PMID: 2413459]
[113]
Namba, T.; Kodama, R.; Moritomo, S.; Hoshino, T.; Mizushima, T. Zidovudine, an anti-viral drug, resensitizes gemcitabine-resistant pancreatic cancer cells to gemcitabine by inhibition of the Akt-GSK3β-Snail pathway. Cell Death Dis., 2015, 6e1795
[http://dx.doi.org/10.1038/cddis.2015.172] [PMID: 26111057]
[114]
Aschacher, T.; Sampl, S.; Käser, L.; Bernhard, D.; Spittler, A.; Holzmann, K.; Bergmann, M. The combined use of known antiviral reverse transcriptase inhibitors AZT and DDI induce anticancer effects at low concentrations. Neoplasia, 2012, 14(1), 44-53.
[http://dx.doi.org/10.1593/neo.11426] [PMID: 22355273]
[115]
Chong, C.R.; Xu, J.; Lu, J.; Bhat, S.; Sullivan, D.J., Jr; Liu, J.O. Inhibition of angiogenesis by the antifungal drug itraconazole. ACS Chem. Biol., 2007, 2(4), 263-270.
[http://dx.doi.org/10.1021/cb600362d] [PMID: 17432820]
[116]
Pounds, R.; Leonard, S.; Dawson, C.; Kehoe, S. Repurposing itraconazole for the treatment of cancer. Oncol. Lett., 2017, 14(3), 2587-2597.
[http://dx.doi.org/10.3892/ol.2017.6569] [PMID: 28927025]
[117]
Pantziarka, P.; Sukhatme, V.; Bouche, G.; Meheus, L.; Sukhatme, V.P. Repurposing drugs in oncology (ReDO)-itraconazole as an anti-cancer agent. Ecancermedicalscience, 2015, 9, 521.
[http://dx.doi.org/10.3332/ecancer.2015.521] [PMID: 25932045]
[118]
Cha, H.J.; Byrom, M.; Mead, P.E.; Ellington, A.D.; Wallingford, J.B.; Marcotte, E.M. Evolutionarily repurposed networks reveal the well-known antifungal drug thiabendazole to be a novel vascular disrupting agent. PLoS Biol., 2012, 10(8)e1001379
[http://dx.doi.org/10.1371/journal.pbio.1001379] [PMID: 22927795]
[119]
Seto, B. Rapamycin and mTOR: a serendipitous discovery and implications for breast cancer. Clin. Transl. Med., 2012, 1(1), 29.
[http://dx.doi.org/10.1186/2001-1326-1-29] [PMID: 23369283]
[120]
Chen, B.; Wei, W.; Ma, L.; Yang, B.; Gill, R.M.; Chua, M.S.; Butte, A.J.; So, S. Computational discovery of niclosamide ethanolamine, a repurposed drug candidate that reduces growth of hepatocellular carcinoma cells in vitro and in mice by inhibiting cell division cycle 37 signaling. Gastroenterology, 2017, 152(8), 2022-2036.
[http://dx.doi.org/10.1053/j.gastro.2017.02.039] [PMID: 28284560]
[121]
Pantziarka, P.; Bouche, G.; Meheus, L.; Sukhatme, V.; Sukhatme, V.P. Repurposing drugs in oncology (ReDO)-mebendazole as an anti-cancer agent. Ecancermedicalscience, 2014, 8, 443.
[http://dx.doi.org/10.3332/ecancer.2014.485] [PMID: 25075217]
[122]
Polascik, T.J.; Mouraviev, V. Zoledronic acid in the management of metastatic bone disease. Ther. Clin. Risk Manag., 2008, 4(1), 261-268.
[http://dx.doi.org/10.2147/TCRM.S2707] [PMID: 18728715]
[123]
Ding, X. Drug screening: Drug repositioning needs a rethink. Nature, 2016, 535(7612), 355.
[http://dx.doi.org/10.1038/535355d] [PMID: 27443733]
[124]
Doudican, N.A.; Kumar, A.; Singh, N.K.; Nair, P.R.; Lala, D.A.; Basu, K.; Talawdekar, A.A.; Sultana, Z.; Tiwari, K.K.; Tyagi, A.; Abbasi, T.; Vali, S.; Vij, R.; Fiala, M.; King, J.; Perle, M.; Mazumder, A. Personalization of cancer treatment using predictive simulation. J. Transl. Med., 2015, 13, 43.
[http://dx.doi.org/10.1186/s12967-015-0399-y] [PMID: 25638213]
[125]
Cheng, F.; Hong, H.; Yang, S.; Wei, Y. Individualized network-based drug repositioning infrastructure for precision oncology in the panomics era. Brief. Bioinform., 2017, 18(4), 682-697.
[PMID: 27296652]
[126]
Hyman, D.M.; Taylor, B.S.; Baselga, J. Implementing genome-driven oncology. Cell, 2017, 168(4), 584-599.
[http://dx.doi.org/10.1016/j.cell.2016.12.015] [PMID: 28187282]
[127]
Rastegar-Mojarad, M.; Liu, H.; Nambisan, P. Using social media data to identify potential candidates for drug repurposing: A feasibility study. JMIR Res. Protoc., 2016, 5(2)e121
[http://dx.doi.org/10.2196/resprot.5621] [PMID: 27311964]

Rights & Permissions Print Cite
Article Metrics
50
4
© 2024 Bentham Science Publishers | Privacy Policy