Abstract
Telomere is the repetitive sequence of non-coding DNA that protects chromosomes from damage. However, with cell division, the length of the telomere gets shortened ultimately leading to cell senescence. Telomere shortening is compensated by the addition of telomeric sequence by telomerase enzyme and thus preventing senescence which may lead to abnormal cell growth and ultimately result in cancer. There might not be a direct effect of telomerase on carcinogenesis, however, the role of telomerase in maintaining the length of telomere and thus tumor growth progression is quite evident. Various studies have reported the significance of telomerase activity in tumor cells. Therefore, targeting the telomerase enzyme can be an effective approach for the management of cancer, and drugs targeting telomerase inhibition are possible therapeutic candidates to be used clinically for the treatment of cancer in the future. Thus, in the current paper, we aim to review various telomerase inhibitors against cancer, challenges in proposing telomerase inhibitors for the treatment of cancer, and future perspectives on developing telomerase inhibitors for the management of cancer.
Graphical Abstract
[http://dx.doi.org/10.1002/ijc.33588] [PMID: 33818764]
[http://dx.doi.org/10.3322/caac.21654] [PMID: 33433946]
[http://dx.doi.org/10.1056/NEJMp1508811] [PMID: 26559569]
[http://dx.doi.org/10.1016/S1387-2656(00)06020-8] [PMID: 11193292]
[http://dx.doi.org/10.1128/MMBR.66.3.407-425.2002]
[http://dx.doi.org/10.1016/j.ebiom.2017.03.027] [PMID: 28347656]
[http://dx.doi.org/10.1161/CIRCRESAHA.118.312202] [PMID: 30355079]
[http://dx.doi.org/10.21775/cimb.035.085] [PMID: 31422934]
[http://dx.doi.org/10.1002/ijc.22473] [PMID: 17311257]
[http://dx.doi.org/10.1111/j.1749-6632.2012.06547.x] [PMID: 22901253]
[http://dx.doi.org/10.3892/mmr.2022.12674] [PMID: 35266017]
[http://dx.doi.org/10.3892/ol.2020.11659] [PMID: 32724340]
[http://dx.doi.org/10.1101/gad.263863.115] [PMID: 26063571]
[http://dx.doi.org/10.3892/or.2013.2665] [PMID: 23933993]
[http://dx.doi.org/10.3390/cells9020359] [PMID: 32033110]
[http://dx.doi.org/10.2147/CIA.S256425] [PMID: 32581523]
[http://dx.doi.org/10.1016/j.ceb.2017.12.001] [PMID: 29253739]
[http://dx.doi.org/10.3390/genes10040318] [PMID: 31022960]
[http://dx.doi.org/10.1007/s00018-019-03369-x] [PMID: 31728577]
[http://dx.doi.org/10.1128/MCB.00240-10] [PMID: 20404094]
[http://dx.doi.org/10.1101/gad.1881810] [PMID: 20231318]
[http://dx.doi.org/10.1038/nsmb.3498] [PMID: 29106411]
[http://dx.doi.org/10.1038/cr.2017.144] [PMID: 29160297]
[http://dx.doi.org/10.1093/nar/gkw846] [PMID: 27655633]
[http://dx.doi.org/10.1038/nature11648] [PMID: 23103865]
[http://dx.doi.org/10.1038/s41580-021-00328-y] [PMID: 33564154]
[http://dx.doi.org/10.1016/j.cell.2012.07.012] [PMID: 22863003]
[http://dx.doi.org/10.1074/jbc.M005962200] [PMID: 11035006]
[http://dx.doi.org/10.1074/jbc.M113.518175] [PMID: 24097987]
[http://dx.doi.org/10.1172/jci.insight.138059] [PMID: 33822766]
[http://dx.doi.org/10.1093/carcin/bgh296] [PMID: 15471900]
[http://dx.doi.org/10.7554/eLife.47333] [PMID: 32297856]
[http://dx.doi.org/10.3892/mmr.2020.11274] [PMID: 32705188]
[http://dx.doi.org/10.1371/journal.pone.0204901] [PMID: 30281650]
[http://dx.doi.org/10.3390/antiox6010017] [PMID: 28264499]
[http://dx.doi.org/10.1038/s41467-020-20474-9] [PMID: 33420056]
[http://dx.doi.org/10.1038/s41429-021-00454-x] [PMID: 34285374]
[http://dx.doi.org/10.1016/j.bmc.2010.08.021] [PMID: 20813535]
[http://dx.doi.org/10.1007/s12038-020-00045-2] [PMID: 32515354]
[http://dx.doi.org/10.1016/j.ijrobp.2019.08.009] [PMID: 31419512]
[http://dx.doi.org/10.3892/etm.2012.471] [PMID: 22969960]
[http://dx.doi.org/10.1590/S0100-879X2010007500143] [PMID: 21180888]
[http://dx.doi.org/10.1126/science.1260200] [PMID: 25722414]
[http://dx.doi.org/10.1038/nrurol.2017.104] [PMID: 28675175]
[http://dx.doi.org/10.1158/0008-5472.CAN-10-0233] [PMID: 21062983]
[http://dx.doi.org/10.1038/ng.3781] [PMID: 28135248]
[http://dx.doi.org/10.1021/jm400528t] [PMID: 24053596]
[http://dx.doi.org/10.1146/annurev.cellbio.22.010305.104518] [PMID: 16824017]
[http://dx.doi.org/10.1093/carcin/bgp268] [PMID: 19887512]
[http://dx.doi.org/10.1016/j.semcancer.2011.10.001] [PMID: 22015685]
[http://dx.doi.org/10.1158/2159-8290.CD-16-0062] [PMID: 27029895]
[http://dx.doi.org/10.1016/j.cell.2011.02.013] [PMID: 21376230]
[http://dx.doi.org/10.1126/science.7605428] [PMID: 7605428]
[http://dx.doi.org/10.1002/j.1460-2075.1995.tb00098.x] [PMID: 7556065]
[http://dx.doi.org/10.1016/S0959-8049(97)00062-2] [PMID: 9282118]
[http://dx.doi.org/10.1038/s41388-020-01405-w]
[http://dx.doi.org/10.1038/sj.neo.7900112] [PMID: 11191109]
[http://dx.doi.org/10.1016/S0959-437X(01)00268-4] [PMID: 11790559]
[http://dx.doi.org/10.3390/biomedicines9050526] [PMID: 34065134]
[http://dx.doi.org/10.3389/fcell.2017.00001] [PMID: 28184371]
[http://dx.doi.org/10.1126/science.276.5312.561] [PMID: 9110970]
[http://dx.doi.org/10.1371/journal.ppat.1003284] [PMID: 23592995]
[http://dx.doi.org/10.3389/fonc.2019.00344] [PMID: 31157162]
[http://dx.doi.org/10.1016/j.mrfmmm.2011.07.006] [PMID: 21802433]
[PMID: 12873987]
[http://dx.doi.org/10.1016/j.jconrel.2010.03.025] [PMID: 20381558]
[http://dx.doi.org/10.1007/s00894-020-04648-2] [PMID: 33415518]
[http://dx.doi.org/10.3390/molecules26020376] [PMID: 33450878]
[http://dx.doi.org/10.1158/0008-5472.CAN-05-1215] [PMID: 16140956]
[http://dx.doi.org/10.18632/oncotarget.9335] [PMID: 27192120]
[http://dx.doi.org/10.1101/158287]
[http://dx.doi.org/10.18632/oncotarget.19410] [PMID: 29137380]
[http://dx.doi.org/10.1016/j.bbrc.2007.06.030] [PMID: 17585882]
[PMID: 12479362]
[http://dx.doi.org/10.3389/fvets.2020.620776] [PMID: 33553285]
[http://dx.doi.org/10.1248/bpb.27.1769] [PMID: 15516720]
[http://dx.doi.org/10.1016/j.fct.2009.04.014] [PMID: 19393284]
[http://dx.doi.org/10.1016/j.phrs.2004.11.003] [PMID: 15749458]
[http://dx.doi.org/10.1074/jbc.M101350200] [PMID: 11441001]
[http://dx.doi.org/10.1074/jbc.M100314200] [PMID: 11335714]
[http://dx.doi.org/10.2174/1389201015666140113112820] [PMID: 24433502]
[http://dx.doi.org/10.2174/1568009616666160426125526] [PMID: 27113744]
[http://dx.doi.org/10.1016/j.bmc.2012.12.020] [PMID: 23321015]
[http://dx.doi.org/10.1002/jcb.23229] [PMID: 21678477]
[http://dx.doi.org/10.1158/2159-8290.CD-14-0609] [PMID: 25516420]
[http://dx.doi.org/10.1016/j.ejmech.2016.02.009] [PMID: 26900656]
[http://dx.doi.org/10.1097/01.ju.0000121329.37206.1b] [PMID: 15076315]
[http://dx.doi.org/10.7314/APJCP.2013.14.6.3449] [PMID: 23886126]
[http://dx.doi.org/10.1080/14756366.2018.1484735] [PMID: 30139286]
[http://dx.doi.org/10.1016/j.ejmech.2019.111891] [PMID: 31759730]
[http://dx.doi.org/10.1039/C5OB01177A] [PMID: 26156660]
[http://dx.doi.org/10.1016/j.jinorgbio.2018.09.004] [PMID: 30265997]
[http://dx.doi.org/10.3390/molecules21111534] [PMID: 27854257]
[http://dx.doi.org/10.1111/jcmm.12412] [PMID: 25256442]
[PMID: 22110194]
[http://dx.doi.org/10.22099/MBRC.2020.38230.1537] [PMID: 33681391]
[http://dx.doi.org/10.1038/sj.onc.1209577] [PMID: 16652154]
[http://dx.doi.org/10.1093/annonc/mdu550] [PMID: 25467017]
[http://dx.doi.org/10.1007/s00018-016-2146-9] [PMID: 26846696]
[http://dx.doi.org/10.1186/s12929-018-0422-8] [PMID: 29526163]
[http://dx.doi.org/10.1016/j.cancergen.2013.10.001] [PMID: 24331919]
[http://dx.doi.org/10.1038/modpathol.3880125] [PMID: 10912930]
[http://dx.doi.org/10.1126/science.aab3389] [PMID: 26785477]
[http://dx.doi.org/10.1016/j.ctrv.2015.02.005] [PMID: 25704912]
[http://dx.doi.org/10.1016/j.bbrc.2014.02.001] [PMID: 24513288]
[http://dx.doi.org/10.1038/sj.leu.2404968] [PMID: 17898784]
[http://dx.doi.org/10.1097/PAT.0b013e3283511cd5] [PMID: 22406483]
[http://dx.doi.org/10.15252/emmm.201910292] [PMID: 31273934]
[http://dx.doi.org/10.1101/gad.246819.114] [PMID: 25128433]
[http://dx.doi.org/10.18632/oncotarget.20542] [PMID: 29113346]
[http://dx.doi.org/10.1038/nature05454] [PMID: 17237768]
[http://dx.doi.org/10.1016/j.lungcan.2009.07.010] [PMID: 19695733]