Abstract
Background: Ovary Carcinoma (OC) is the most lethal gynecological neoplasm due to the late diagnoses and to the common development of resistance to platinum-based chemotherapy. Thus, novel therapeutic approaches are urgently required. In this regard, the strategy of drug repurposing is becoming attractive. By this approach, the effectiveness of a drug originally developed for another indication is tested in a different pathology. The advantage is that data about pharmacokinetic properties and toxicity are already available. Thus, in principle, it is possible to reduce research costs and to speed up drug usage/marketing.
Results: Here, some noticeable examples of repurposed drugs for OC, such as amiodarone, ruxolitinib, statins, disulfiram, ormeloxifenem, and Quinacrine, are reported. Amiodarone, an antiarrhythmic agent, has shown promising anti-OC activity, although the systemic toxicity should not be neglected. The JAK inhibitor, Ruxolitinib, may be employed particularly in coadministration with standard OC therapy as it synergistically interacts with platinum-based drugs. Particularly interesting is the use of statin which represent one of the most commonly administered drugs in aged population to treat hypercholesterolemia. Disulfiram, employed in the treatment of chronic alcoholism, has shown anti-OC properties. Ormeloxifene, commonly used for contraception, seems to be promising, especially due to the negligible side effects. Finally, Quinacrine used as an antimicrobial and anti-inflammatory drug, is able to downregulate OC cell growth and promote cell death.
Conclusion: Whereas further testing in patients are necessary to better clarify the therapeutic potential of repurposed drugs for OC, it is believed that their use, better if combined with OC targeted delivery systems, can significantly contribute to the development of novel and effective anti-OC treatments.
Keywords: Drug repurposing, ovarian cancer, amiodarone, ruxolitinib, statins, disulfiram, ormeloxifene.
[http://dx.doi.org/10.1016/j.bpobgyn.2016.08.006] [PMID: 27743768]
[http://dx.doi.org/10.1097/IGC.0000000000001118] [PMID: 29278600]
[http://dx.doi.org/10.1038/nrdp.2016.61] [PMID: 27558151]
[http://dx.doi.org/10.1016/S0002-9440(10)63708-X] [PMID: 15111296]
[http://dx.doi.org/10.1172/JCI65833] [PMID: 23257362]
[http://dx.doi.org/10.1093/jnci/dju249] [PMID: 25269487]
[http://dx.doi.org/10.1158/1078-0432.CCR-17-0246] [PMID: 28280090]
[http://dx.doi.org/10.1038/nature10166] [PMID: 21720365]
[http://dx.doi.org/10.1038/nrclinonc.2015.224] [PMID: 26787282]
[http://dx.doi.org/10.1200/JCO.2014.59.4945] [PMID: 25964255]
[http://dx.doi.org/10.3390/ijms20040952] [PMID: 30813239]
[http://dx.doi.org/10.1016/S0889-8588(03)00058-3]
[http://dx.doi.org/10.1200/JCO.1992.10.5.706] [PMID: 1569443]
[http://dx.doi.org/10.1016/S0140-6736(02)09738-6] [PMID: 12241653]
[http://dx.doi.org/10.1093/annonc/mdx451] [PMID: 29232474]
[http://dx.doi.org/10.1038/nrc2644] [PMID: 19461667]
[http://dx.doi.org/10.1080/14737159.2017.1326820] [PMID: 28468520]
[http://dx.doi.org/10.3390/cancers12051175] [PMID: 32392708]
[http://dx.doi.org/10.1186/s12967-016-1027-1] [PMID: 27634150]
[http://dx.doi.org/10.1038/s41392-019-0055-8]
[http://dx.doi.org/10.1038/s41392-018-0026-5] [PMID: 30174831]
[http://dx.doi.org/10.1016/j.ygyno.2018.09.019] [PMID: 30301560]
[http://dx.doi.org/10.1038/onc.2017.328] [PMID: 28967908]
[http://dx.doi.org/10.1158/1535-7163.MCT-14-0801] [PMID: 26227489]
[http://dx.doi.org/10.1038/nrc.2017.53] [PMID: 28751651]
[http://dx.doi.org/10.1038/ncomms3126] [PMID: 23839242]
[http://dx.doi.org/10.1016/S0735-1097(97)00220-9] [PMID: 9283542]
[http://dx.doi.org/10.3389/fonc.2016.00142] [PMID: 27379204]
[http://dx.doi.org/10.1158/0008-5472.CAN-07-0858] [PMID: 17974982]
[http://dx.doi.org/10.1002/mrm.26876] [PMID: 28833401]
[http://dx.doi.org/10.18632/oncotarget.24368] [PMID: 29849942]
[http://dx.doi.org/10.2147/TCRM.S23277] [PMID: 22399854]
[http://dx.doi.org/10.14797/mdcj-15-1-23 ] [PMID: 31049146]
[http://dx.doi.org/10.1161/ATVBAHA.108.179564] [PMID: 19299327]
[http://dx.doi.org/10.1038/343425a0] [PMID: 1967820]
[http://dx.doi.org/10.1016/j.cell.2011.12.017] [PMID: 22265415]
[http://dx.doi.org/10.1158/1078-0432.CCR-14-3368] [PMID: 26109099]
[http://dx.doi.org/10.1038/nrd2221] [PMID: 17585331]
[http://dx.doi.org/10.1038/nrc3379] [PMID: 23076158]
[http://dx.doi.org/10.18632/oncotarget.5834] [PMID: 26503475]
[http://dx.doi.org/10.3390/medicines5010016] [PMID: 29389895]
[http://dx.doi.org/10.18632/oncotarget.10121] [PMID: 27329838]
[http://dx.doi.org/10.1161/CIRCULATIONAHA.106.624890] [PMID: 17159064]
[http://dx.doi.org/10.1517/14740338.2011.540568] [PMID: 21342078]
[http://dx.doi.org/10.1097/01.jcp.0000222512.25649.08] [PMID: 16702894]
[http://dx.doi.org/10.1097/CEJ.0b013e3283647466] [PMID: 23863824]
[http://dx.doi.org/10.18632/oncotarget.969] [PMID: 23594434]
[http://dx.doi.org/10.18632/oncoscience.5] [PMID: 25593981]
[http://dx.doi.org/10.1158/0008-5472.CAN-06-1567] [PMID: 17234771]
[http://dx.doi.org/10.3892/or.2017.5525] [PMID: 28339059]
[PMID: 96021]
[http://dx.doi.org/10.1016/j.lfs.2007.11.028] [PMID: 18279897]
[http://dx.doi.org/10.1016/j.bbrc.2010.11.049] [PMID: 21094138]
[http://dx.doi.org/10.1002/pmic.201000720] [PMID: 21360677]
[http://dx.doi.org/10.1002/med.1011] [PMID: 11410933]
[http://dx.doi.org/10.1016/j.canlet.2014.10.009] [PMID: 25306892]
[http://dx.doi.org/10.1038/s41598-018-20541-8] [PMID: 29396506]
[http://dx.doi.org/10.1002/ddr.21440] [PMID: 30284735]
[http://dx.doi.org/10.1016/j.semcancer.2019.09.021] [PMID: 31562955]
[http://dx.doi.org/10.1073/pnas.0508888102] [PMID: 16287968]
[http://dx.doi.org/10.1038/s41598-018-20531-w] [PMID: 29410485]
[http://dx.doi.org/10.1016/0168-8278(95)80198-7] [PMID: 8655957]
[http://dx.doi.org/10.1038/bjc.2011.500] [PMID: 22095224]
[http://dx.doi.org/10.3390/pharmaceutics11100547] [PMID: 31652539]
[http://dx.doi.org/10.1016/j.lwt.2016.01.025]
[http://dx.doi.org/10.2174/1389200216666150206124913] [PMID: 25658127]
[http://dx.doi.org/10.3390/molecules23040777] [PMID: 29597300]
[http://dx.doi.org/10.1080/17425247.2017.1292247] [PMID: 28266887]
[http://dx.doi.org/10.1016/j.ijpharm.2017.01.034] [PMID: 28119125]