Abstract
The costs of developing, validating and buying new drugs are dramatically increasing. On the other hand, sobering economies have difficulties in sustaining their healthcare systems, particularly in countries with an elderly population requiring increasing welfare. This conundrum requires immediate action, and a possible option is to study the large, already present arsenal of drugs approved and to use them for innovative therapies. This possibility is particularly interesting in oncology, where the complexity of the cancer genome dictates in most patients a multistep therapeutic approach. In this review, we discuss a) Computational approaches; b) preclinical models; c) currently ongoing or already published clinical trials in the drug repurposing field in oncology; and d) drug repurposing to overcome resistance to previous therapies.
Keywords: Oncology, drug, repurposing, in silico, computational approaches, preclinical models, therapies.
[http://dx.doi.org/10.1038/nrclinonc.2015.169] [PMID: 26483297]
[http://dx.doi.org/10.1038/nrd.2018.168] [PMID: 30310233]
[http://dx.doi.org/10.1097/PPO.0000000000000360] [PMID: 30896529]
[http://dx.doi.org/10.1016/j.semcancer.2019.09.023] [PMID: 31562957.]
[http://dx.doi.org/10.1016/j.coph.2019.12.004] [PMID: 31982325]
[http://dx.doi.org/10.1038/clpt.2012.96] [PMID: 22992668]
[http://dx.doi.org/10.1093/nar/gkv1075] [PMID: 26481350]
[http://dx.doi.org/10.1093/nar/gkj067] [PMID: 16381955]
[http://dx.doi.org/10.1093/nar/gkx1089] [PMID: 29140435]
[http://dx.doi.org/10.1093/nar/gkw1072] [PMID: 27903890]
[http://dx.doi.org/10.1126/science.1132939] [PMID: 17008526]
[http://dx.doi.org/10.1073/pnas.0506580102] [PMID: 16199517]
[http://dx.doi.org/10.1016/j.cels.2017.11.001] [PMID: 29199020]
[http://dx.doi.org/10.3389/fonc.2019.01503] [PMID: 31993373]
[http://dx.doi.org/10.1093/nar/gku368] [PMID: 24813447]
[http://dx.doi.org/10.1093/bioinformatics/btx454] [PMID: 29036271]
[http://dx.doi.org/10.1093/bioinformatics/bty845] [PMID: 30304355]
[http://dx.doi.org/10.1186/1471-2105-10-236] [PMID: 19646231]
[http://dx.doi.org/10.1093/nar/gkv445] [PMID: 25940629]
[http://dx.doi.org/10.1186/s12864-016-2737-8] [PMID: 27234029]
[http://dx.doi.org/10.1093/nar/gkv1070] [PMID: 26476454]
[http://dx.doi.org/10.1093/bioinformatics/btz006] [PMID: 30624606]
[http://dx.doi.org/10.1073/pnas.1000138107] [PMID: 20679242]
[http://dx.doi.org/10.1093/bioinformatics/btu058] [PMID: 24558125]
[http://dx.doi.org/10.1158/0008-5472.CAN-17-0096] [PMID: 28314784]
[http://dx.doi.org/10.1158/2159-8290.CD-15-0235] [PMID: 26482930]
[http://dx.doi.org/10.1038/nrc1951] [PMID: 16990858]
[http://dx.doi.org/10.1093/bioinformatics/bty133] [PMID: 29534151]
[http://dx.doi.org/10.1038/ng.3314] [PMID: 26121088]
[http://dx.doi.org/10.1371/journal.pgen.1008489] [PMID: 31830040]
[http://dx.doi.org/10.1093/bioinformatics/btq126] [PMID: 20335276]
[http://dx.doi.org/10.1186/s10020-019-0098-x] [PMID: 31221082]
[http://dx.doi.org/10.1038/nature24284] [PMID: 29059683]
[http://dx.doi.org/10.1016/j.ajhg.2017.12.005] [PMID: 29304378]
[http://dx.doi.org/10.1038/s41586-020-1969-6]
[http://dx.doi.org/10.1038/s41586-020-1965-x] [PMID: 32025015]
[http://dx.doi.org/10.1038/s41586-020-1943-3] [PMID: 32025018]
[http://dx.doi.org/10.1038/s41586-019-1913-9] [PMID: 32025012]
[http://dx.doi.org/doi.org/10.1038/s41586-019-1907-7] [PMID: 32025013 ]
[http://dx.doi.org/10.1038/s41586-020-1970-0] [PMID: 32025019]
[http://dx.doi.org/10.1186/1758-2946-5-30] [PMID: 23800010]
[http://dx.doi.org/10.1371/journal.pone.0150460] [PMID: 26954019]
[http://dx.doi.org/10.1186/s12859-018-2123-4] [PMID: 29642848]
[http://dx.doi.org/10.1038/s41598-017-18315-9] [PMID: 29317676]
[http://dx.doi.org/10.1093/bioinformatics/btz156] [PMID: 30840053]
[http://dx.doi.org/10.1089/omi.2019.0096] [PMID: 31895625]
[http://dx.doi.org/10.1124/pr.110.003293] [PMID: 21415126]
[http://dx.doi.org/10.1111/acel.12626] [PMID: 28620943]
[http://dx.doi.org/10.1093/emph/eow014] [PMID: 27121451]
[http://dx.doi.org/10.1016/0959-8049(95)00181-H] [PMID: 7576992]
[http://dx.doi.org/10.1182/blood.V89.2.376] [PMID: 9002938]
[http://dx.doi.org/10.1073/pnas.97.7.3444] [PMID: 10716706]
[http://dx.doi.org/10.1182/blood-2016-01-643569] [PMID: 26980727]
[PMID: 1808819]
[http://dx.doi.org/10.1111/bjh.12708] [PMID: 24328678]
[http://dx.doi.org/10.1038/nsmb.2874] [PMID: 25108355]
[http://dx.doi.org/10.1038/nature13527] [PMID: 25043012]
[http://dx.doi.org/10.1126/science.1244917] [PMID: 24292623]
[http://dx.doi.org/10.1182/blood-2018-05-852798] [PMID: 30064974]
[http://dx.doi.org/10.1001/jama.2012.7422] [PMID: 9669771]
[http://dx.doi.org/10.2174/156802607779941198] [PMID: 17305584]
[http://dx.doi.org/10.1054/blre.2001.0157] [PMID: 11735159]
[http://dx.doi.org/10.1016/j.stemcr.2019.09.004] [PMID: 31607567]
[http://dx.doi.org/10.1016/j.euroneuro.2017.04.003] [PMID: 28579071]
[http://dx.doi.org/10.3389/fonc.2018.00255] [PMID: 30073149]
[http://dx.doi.org/10.1038/s41375-018-0375-7] [PMID: 30679800]
[http://dx.doi.org/10.1126/sciadv.aax2746] [PMID: 32284990]
[http://dx.doi.org/10.1016/S0959-8049(02)00040-0] [PMID: 11978510]
[http://dx.doi.org/10.1592/phco.30.12.1266] [PMID: 21114394]
[http://dx.doi.org/10.1038/nchembio.2510] [PMID: 29083417]
[http://dx.doi.org/10.3399/bjgp16X684433] [PMID: 27033477]
[http://dx.doi.org/10.3892/ol.2018.8098] [PMID: 29616131]
[http://dx.doi.org/10.1016/j.ajpath.2017.04.022] [PMID: 28733194]
[http://dx.doi.org/10.1016/0002-9343(90)90534-K] [PMID: 2189310]
[http://dx.doi.org/10.18632/oncotarget.2166] [PMID: 25277186]
[http://dx.doi.org/10.1038/nature25016] [PMID: 29211715]
[http://dx.doi.org/10.1042/CS20110386] [PMID: 22117616]
[http://dx.doi.org/10.1186/s13046-019-1211-2] [PMID: 31164151]
[http://dx.doi.org/10.3389/fonc.2017.00193] [PMID: 28894699]
[http://dx.doi.org/10.1111/j.1582-4934.2001.tb00172.x] [PMID: 12067471]
[http://dx.doi.org/10.1038/srep44841] [PMID: 28344327]
[http://dx.doi.org/10.7150/ijbs.23542] [PMID: 29725262]
[http://dx.doi.org/10.1038/sj.bjc.6604554] [PMID: 18766181]
[http://dx.doi.org/10.1155/2019/8201079]] [PMID: 31827705]
[http://dx.doi.org/10.1002/2211-5463.12628] [PMID: 30973680]
[http://dx.doi.org/10.18632/oncotarget.16991] [PMID: 28881758]
[http://dx.doi.org/10.1158/1535-7163.MCT-18-0063] [PMID: 29907593]
[http://dx.doi.org/10.2147/CMAR.S156530] [PMID: 29844702]
[http://dx.doi.org/10.1007/s11060-011-0749-4] [PMID: 22045118]
[http://dx.doi.org/10.1056/NEJMoa043330 ] [PMID: 15758009]
[http://dx.doi.org/10.18632/oncotarget.707] [PMID: 23165409]
[http://dx.doi.org/10.18632/oncotarget.604] [PMID: 23047041]
[http://dx.doi.org/10.1038/bjc.2012.442] [PMID: 23033007]
[http://dx.doi.org/doi.org/10.3332/ecancer.2017.781] [PMID: 29225688 ]
[http://dx.doi.org/10.7326/0003-4819-144-5-200603070-00008] [PMID: 16520474]
[http://dx.doi.org/10.7326/0003-4819-144-5-200603070-00015] [PMID: 16520480]
[http://dx.doi.org/10.1007/s00066-014-0693-2] [PMID: 24928248]
[http://dx.doi.org/10.1186/1748-717X-8-209] [PMID: 24010771]
[http://dx.doi.org/10.1016/S0140-6736(09)61964-4] [PMID: 20113825]
[http://dx.doi.org/10.1016/j.jbo.2013.12.001] [PMID: 26909294]
[http://dx.doi.org/10.1177/1758835919853971] [PMID: 31210800]
[http://dx.doi.org/10.1023/A:1024491219366] [PMID: 12889599]
[http://dx.doi.org/10.1200/JCO.2010.33.5422] [PMID: 21632503]
[http://dx.doi.org/10.1016/j.pharmthera.2011.09.004] [PMID: 21924289]
[http://dx.doi.org/10.1073/pnas.1417636112] [PMID: 25624476]
[http://dx.doi.org/10.1158/1940-6207.CAPR-10-0055] [PMID: 20810672]
[http://dx.doi.org/10.1016/S0140-6736(16)30958-8] [PMID: 27574741]
[http://dx.doi.org/10.1001/jamaoncol.2019.2553] [PMID: 31486833]
[http://dx.doi.org/doi.org/10.1016/j.semcancer.2009.05.003] [PMID: 19482086]
[http://dx.doi.org/10.1016/j.ejca.2009.04.007] [PMID: 19406633]
[http://dx.doi.org/10.1038/bjc.2012.406] [PMID: 22990652]
[http://dx.doi.org/10.1016/S0140-6736(14)60845-X] [PMID: 24933332]
[http://dx.doi.org/10.1016/S0140-6736(11)60545-X] [PMID: 21621716]
[http://dx.doi.org/10.1186/s12885-019-5676-3] [PMID: 31138229]
[http://dx.doi.org/10.1200/JCO.2005.06.027] [PMID: 15632409]
[http://dx.doi.org/10.1182/blood-2010-02-269837] [PMID: 20668229]
[http://dx.doi.org/10.3390/cancers12020441] [PMID: 32069925]
[http://dx.doi.org/10.1038/nm.2661] [PMID: 22406747]
[http://dx.doi.org/10.1101/cshperspect.a033415] [PMID: 28710258]
[http://dx.doi.org/10.1038/s41586-019-1730-1] [PMID: 31723286]
[http://dx.doi.org/doi.org/10.3332/ecancer.2014.442] [PMID: 25075216 ]
[http://dx.doi.org/10.1038/nrclinonc.2013.158] [PMID: 23999218]
[PMID: 10766175]
[http://dx.doi.org/10.1038/nrc1369] [PMID: 15170445]
[http://dx.doi.org/10.1038/nrc1971] [PMID: 17036040]
[http://dx.doi.org/10.1038/nrc.2017.51] [PMID: 28706266]
[http://dx.doi.org/10.1016/j.trecan.2017.03.011] [PMID: 28718409]
[http://dx.doi.org/10.1084/jem.20151665] [PMID: 27881732]
[http://dx.doi.org/10.1007/s00262-006-0225-8] [PMID: 16960692]
[http://dx.doi.org/doi.org/10.1016/S0140-6736(13)61777-8] [PMID: 23972812]
[http://dx.doi.org/10.3332/ecancer.2015.499] [PMID: 25624880]
[http://dx.doi.org/10.18632/oncotarget.13760] [PMID: 27926515]
[http://dx.doi.org/10.1016/j.breast.2005.08.026] [PMID: 16199161]
[http://dx.doi.org/10.3390/ijms18081786] [PMID: 28817103]
[PMID: 32194900]
[http://dx.doi.org/10.1172/jci.insight.130748] [PMID: 31600167]
[http://dx.doi.org/10.1016/j.canlet.2018.01.050] [PMID: 29414305]
[http://dx.doi.org/10.1038/s41416-018-0076-z] [PMID: 29695766]
[http://dx.doi.org/10.1109/JBHI.2015.2412522] [PMID: 25781964]
[http://dx.doi.org/10.1186/s40169-018-0185-6] [PMID: 29541939]
[http://dx.doi.org/10.3390/jpm8040036] [PMID: 30400625]
[http://dx.doi.org/10.1186/gm326] [PMID: 22494857]
[http://dx.doi.org/10.1093/annonc/mdw305] [PMID: 27573756]
[http://dx.doi.org/10.1634/theoncologist.2009-0317] [PMID: 20688807]
[http://dx.doi.org/10.26633/RPSP.2020.40] [PMID: 32256547]
[http://dx.doi.org/10.2217/imt.13.33] [PMID: 23638746]
[http://dx.doi.org/10.1016/j.ejca.2016.09.010] [PMID: 27755997]
[http://dx.doi.org/10.1101/gad.314617.118] [PMID: 30275043]
[http://dx.doi.org/doi.org/10.1016/j.semcancer.2015.03.004] [PMID: 25818339]
[http://dx.doi.org/10.1007/s00428-018-2477-z] [PMID: 30374798]
[http://dx.doi.org/10.1016/j.adro.2018.08.018] [PMID: 30370351]
[http://dx.doi.org/10.3389/fimmu.2019.01084] [PMID: 31178859]
[http://dx.doi.org/10.2217/imt-2018-0006] [PMID: 30073897]
[http://dx.doi.org/10.18632/oncotarget.17061] [PMID: 28467800]
[http://dx.doi.org/10.1158/1078-0432.CCR-16-3122] [PMID: 28341752]
[http://dx.doi.org/10.1016/j.ejphar.2018.06.017] [PMID: 29920284]
[http://dx.doi.org/10.1038/s41467-019-12384-2] [PMID: 31554795]
[http://dx.doi.org/10.1038/s41598-017-15348-y] [PMID: 29116249]
[http://dx.doi.org/10.1038/nm.3337] [PMID: 24056773]
[http://dx.doi.org/10.1016/j.semcancer.2019.12.011] [PMID: 31904426]
[http://dx.doi.org/10.1038/cr.2016.151] [PMID: 27995907]
[http://dx.doi.org/10.1111/imm.12913] [PMID: 29460448]
[http://dx.doi.org/10.1158/1078-0432.CCR-17-0895] [PMID: 28855352]
[http://dx.doi.org/10.1177/2515135520904238] [PMID: 32206744]
[http://dx.doi.org/10.4110/in.2020.20.e2] [PMID: 32158590]
[http://dx.doi.org/10.3389/fcell.2020.00017] [PMID: 32117960]
[http://dx.doi.org/10.1016/j.celrep.2019.10.119] [PMID: 31801090]
[http://dx.doi.org/10.2174/0929867324666170712160621] [PMID: 28707587]
[http://dx.doi.org/10.1371/journal.pone.0180297] [PMID: 28672024]
[http://dx.doi.org/10.1007/s10549-019-05183-2] [PMID: 30852762]
[http://dx.doi.org/10.1007/s11060-016-2104-2 ] [PMID: 26966095]
[http://dx.doi.org/doi.org/10.1007/s10637-017-0511-7] [PMID: 28936567]