Abstract
Cancer is increasingly recognized as one of the primary causes of death and has become a multifaceted global health issue. Modern medical science has made significant advancements in the diagnosis and therapy of cancer over the past decade. The detrimental side effects, lack of efficacy, and multidrug resistance of conventional cancer therapies have created an urgent need for novel anticancer therapeutics or treatments with low cytotoxicity and drug resistance. The pharmaceutical groups have recognized the crucial role that peptide therapeutic agents can play in addressing unsatisfied healthcare demands and how these become great supplements or even preferable alternatives to biological therapies and small molecules. Anticancer peptides, as a vibrant therapeutic strategy against various cancer cells, have demonstrated incredible anticancer potential due to high specificity and selectivity, low toxicity, and the ability to target the surface of traditional “undruggable” proteins. This review will provide the research progression of anticancer peptides, mainly focusing on the discovery and modifications along with the optimization and application of these peptides in clinical practice.
[http://dx.doi.org/10.1039/D0NP00019A] [PMID: 32776055]
[http://dx.doi.org/10.1098/rsob.200004] [PMID: 32692959]
[http://dx.doi.org/10.3389/fchem.2017.00005] [PMID: 28271058]
[http://dx.doi.org/10.2147/CMAR.S232708] [PMID: 32021452]
[http://dx.doi.org/10.1038/s41573-020-00135-8] [PMID: 33536635]
[http://dx.doi.org/10.1038/d41573-022-00001-9] [PMID: 34983958]
[http://dx.doi.org/10.2174/18755305MTEygMzc63] [PMID: 33319654]
[http://dx.doi.org/10.3390/molecules25061285] [PMID: 32178315]
[http://dx.doi.org/10.1016/j.peptides.2021.170608] [PMID: 34265369]
[http://dx.doi.org/10.1038/s41589-021-00892-6] [PMID: 34811516]
[http://dx.doi.org/10.1016/j.tetlet.2003.11.112]
[http://dx.doi.org/10.1007/s11418-021-01542-w] [PMID: 34244894]
[http://dx.doi.org/10.2174/1568026619666190125161517] [PMID: 30686254]
[http://dx.doi.org/10.1021/jo0478858] [PMID: 15822975]
[http://dx.doi.org/10.1021/np010049y] [PMID: 11473421]
[http://dx.doi.org/10.1021/ja00256a070]
[http://dx.doi.org/10.1039/C9OB01639B] [PMID: 31460552]
[http://dx.doi.org/10.3892/ijo.31.2.353] [PMID: 17611692]
[http://dx.doi.org/10.1080/19420862.2019.1703531] [PMID: 31847708]
[http://dx.doi.org/10.1056/NEJMoa2115304] [PMID: 34904799]
[PMID: 29671468]
[http://dx.doi.org/10.1073/pnas.85.12.4118] [PMID: 3380783]
[http://dx.doi.org/10.1038/nchembio.1797] [PMID: 25867045]
[http://dx.doi.org/10.1093/annonc/mdl165] [PMID: 16966366]
[http://dx.doi.org/10.1111/bph.14876] [PMID: 31621891]
[http://dx.doi.org/10.1126/science.abf4058] [PMID: 33495306]
[http://dx.doi.org/10.1158/1078-0432.CCR-14-0914] [PMID: 26199389]
[http://dx.doi.org/10.1016/S1470-2045(18)30147-5] [PMID: 29706375]
[http://dx.doi.org/10.3390/ijms19103041] [PMID: 30301180]
[http://dx.doi.org/10.1371/journal.pone.0094122] [PMID: 24713808]
[http://dx.doi.org/10.1385/IR:31:2:075] [PMID: 15778507]
[http://dx.doi.org/10.1016/j.bbamcr.2014.11.006] [PMID: 25447543]
[http://dx.doi.org/10.1111/jcmm.13745] [PMID: 29993185]
[http://dx.doi.org/10.1016/j.jprot.2013.05.022] [PMID: 23727489]
[http://dx.doi.org/10.1073/pnas.0900947106] [PMID: 19255450]
[http://dx.doi.org/10.1016/j.canlet.2013.06.016] [PMID: 23792224]
[http://dx.doi.org/10.1073/pnas.1008930107] [PMID: 20660730]
[http://dx.doi.org/10.1021/jm3005465] [PMID: 22694121]
[http://dx.doi.org/10.1111/bjd.17634] [PMID: 30637717]
[http://dx.doi.org/10.1021/jacs.9b09106] [PMID: 31752491]
[http://dx.doi.org/10.1038/s41467-020-18711-2] [PMID: 33004797]
[http://dx.doi.org/10.1002/cbic.201500525] [PMID: 26677067]
[http://dx.doi.org/10.3109/21691401.2016.1167705] [PMID: 27068253]
[http://dx.doi.org/10.1016/j.bbrc.2016.12.156] [PMID: 28025143]
[http://dx.doi.org/10.1038/s41598-019-47568-9] [PMID: 31375699]
[http://dx.doi.org/10.1016/j.bbrc.2011.03.030] [PMID: 21396910]
[http://dx.doi.org/10.1039/C7OB02233F] [PMID: 29090725]
[http://dx.doi.org/10.1016/j.biocel.2018.05.013] [PMID: 29800725]
[http://dx.doi.org/10.1021/bc300537z] [PMID: 23241015]
[http://dx.doi.org/10.1016/j.bmcl.2017.09.014] [PMID: 28916339]
[http://dx.doi.org/10.1124/jpet.108.146431] [PMID: 19038778]
[http://dx.doi.org/10.1073/pnas.1413185112] [PMID: 25624485]
[http://dx.doi.org/10.1016/j.apsb.2021.06.013] [PMID: 34589388]
[http://dx.doi.org/10.1016/j.bmc.2018.05.014] [PMID: 29807699]
[http://dx.doi.org/10.1111/cbdd.12667] [PMID: 26390861]
[http://dx.doi.org/10.1039/C7SC02616A] [PMID: 29163910]
[http://dx.doi.org/10.1021/acs.bioconjchem.0c00355] [PMID: 32786366]
[http://dx.doi.org/10.1002/(SICI)1097-0215(19991029)83:3<326::AID-IJC7>3.0.CO;2-X] [PMID: 10495424]
[http://dx.doi.org/10.1021/acs.molpharmaceut.8b00605] [PMID: 30183307]
[http://dx.doi.org/10.1021/ja210569f] [PMID: 22413859]
[http://dx.doi.org/10.1371/journal.pone.0138911] [PMID: 26405806]
[http://dx.doi.org/10.1200/JCO.2011.37.4223] [PMID: 22271479]
[http://dx.doi.org/10.1021/acs.jnatprod.6b00051] [PMID: 26980238]
[http://dx.doi.org/10.1186/s12885-016-3003-9] [PMID: 28061765]
[http://dx.doi.org/10.2147/IJN.S76104] [PMID: 26082634]
[http://dx.doi.org/10.3390/toxins7062159] [PMID: 26110505]
[http://dx.doi.org/10.1074/jbc.M800776200] [PMID: 18579526]
[http://dx.doi.org/10.1007/s00018-018-2897-6] [PMID: 30109357]
[http://dx.doi.org/10.1021/acs.jproteome.5b00630] [PMID: 26322961]
[http://dx.doi.org/10.1093/gbe/evw149] [PMID: 27412610]
[http://dx.doi.org/10.1016/j.jprot.2017.07.007] [PMID: 28739511]
[http://dx.doi.org/10.1021/acs.chemrev.8b00430] [PMID: 30395448]
[http://dx.doi.org/10.1126/science.4001944] [PMID: 4001944]
[http://dx.doi.org/10.1080/1061186X.2016.1258570] [PMID: 27819143]
[http://dx.doi.org/10.1007/s13238-019-0639-7] [PMID: 31140150]
[http://dx.doi.org/10.1016/j.drudis.2013.09.001] [PMID: 24051398]
[http://dx.doi.org/10.1517/17460441.2015.1037738] [PMID: 25910798]
[http://dx.doi.org/10.1016/j.cbpa.2015.02.008] [PMID: 25768886]
[http://dx.doi.org/10.1126/science.271.5257.1854] [PMID: 8596952]
[http://dx.doi.org/10.1073/pnas.94.23.12297] [PMID: 9356443]
[http://dx.doi.org/10.1038/nprot.2011.331] [PMID: 21637198]
[http://dx.doi.org/10.1038/nmeth877] [PMID: 16628205]
[http://dx.doi.org/10.1038/s41557-019-0278-x] [PMID: 31182821]
[http://dx.doi.org/10.1038/354082a0] [PMID: 1944576]
[http://dx.doi.org/10.1021/acs.orglett.8b00717] [PMID: 29617143]
[http://dx.doi.org/10.1038/s41467-021-24597-5] [PMID: 34301935]
[http://dx.doi.org/10.1021/acs.joc.9b02396] [PMID: 31799848]
[http://dx.doi.org/10.1038/nm0103-118] [PMID: 12514724]
[http://dx.doi.org/10.1248/cpb.c15-00282] [PMID: 26040271]
[http://dx.doi.org/10.1080/17460441.2019.1551355] [PMID: 30518273]
[http://dx.doi.org/10.1016/j.bmc.2019.02.043] [PMID: 30846404]
[http://dx.doi.org/10.1093/nar/gkr431] [PMID: 21622962]
[http://dx.doi.org/10.1371/journal.pone.0018934] [PMID: 21572516]
[http://dx.doi.org/10.1093/nar/gkv495] [PMID: 25969449]
[http://dx.doi.org/10.1093/nar/gkv456] [PMID: 25943545]
[http://dx.doi.org/10.1016/j.biomaterials.2017.11.024] [PMID: 29182932]
[http://dx.doi.org/10.3389/fgene.2021.698477] [PMID: 34276801]
[http://dx.doi.org/10.3390/ijms20081964] [PMID: 31013619]
[http://dx.doi.org/10.1038/srep02984] [PMID: 24136089]
[http://dx.doi.org/10.18632/oncotarget.7815] [PMID: 26942877]
[http://dx.doi.org/10.1093/bioinformatics/bty451] [PMID: 29868903]
[http://dx.doi.org/10.3390/molecules24101973] [PMID: 31121946]
[http://dx.doi.org/10.1038/s41598-021-02703-3] [PMID: 34880291]
[http://dx.doi.org/10.1007/s10989-014-9435-7]
[http://dx.doi.org/10.1016/j.omtn.2019.04.025] [PMID: 31173946]
[http://dx.doi.org/10.3389/fgene.2020.00760] [PMID: 32903636]
[http://dx.doi.org/10.1093/bib/bbz088] [PMID: 31729528]
[http://dx.doi.org/10.1007/s10989-021-10222-y]
[http://dx.doi.org/10.7717/peerj.11906] [PMID: 34414035]
[http://dx.doi.org/10.1016/j.csbj.2015.11.005]
[http://dx.doi.org/10.1016/j.ejmech.2019.111844] [PMID: 31706640]
[http://dx.doi.org/10.1021/acs.jmedchem.7b00318] [PMID: 28737935]
[http://dx.doi.org/10.1007/s00726-017-2453-y] [PMID: 28664269]
[http://dx.doi.org/10.1002/med.20252] [PMID: 21922503]
[http://dx.doi.org/10.1002/prot.21629] [PMID: 17876818]
[http://dx.doi.org/10.2220/biomedres.37.153] [PMID: 27108884]
[http://dx.doi.org/10.1111/cbdd.12564] [PMID: 25845421]
[http://dx.doi.org/10.1021/jacs.7b10254] [PMID: 29283563]
[http://dx.doi.org/10.1016/j.yexmp.2015.08.021] [PMID: 26344617]
[http://dx.doi.org/10.1080/21553769.2019.1622596]
[http://dx.doi.org/10.1074/jbc.M110.116814] [PMID: 20382735]
[http://dx.doi.org/10.3390/ijms22168677] [PMID: 34445382]
[http://dx.doi.org/10.1046/j.1397-002x.2001.10994.x] [PMID: 11906604]
[http://dx.doi.org/10.1074/jbc.M116.759837] [PMID: 27923812]
[http://dx.doi.org/10.1074/jbc.M211204200] [PMID: 12646578]
[http://dx.doi.org/10.1021/bi027212o] [PMID: 12899621]
[http://dx.doi.org/10.1016/j.bmc.2017.09.040] [PMID: 29029900]
[http://dx.doi.org/10.1021/jm200278m] [PMID: 21688787]
[http://dx.doi.org/10.1016/j.ejmech.2007.06.008] [PMID: 17692431]
[http://dx.doi.org/10.1021/jm800156z] [PMID: 18666771]
[http://dx.doi.org/10.1002/ejoc.201800803]
[http://dx.doi.org/10.1016/j.bmc.2016.06.048] [PMID: 27387357]
[http://dx.doi.org/10.1021/jm5010896] [PMID: 25207470]
[http://dx.doi.org/10.1021/ja809508f] [PMID: 19239270]
[http://dx.doi.org/10.1208/s12248-014-9687-3] [PMID: 25366889]
[http://dx.doi.org/10.1038/nchem.1062] [PMID: 21697871]
[http://dx.doi.org/10.1021/ja000563a]
[http://dx.doi.org/10.1126/scitranslmed.aao3003] [PMID: 29643228]
[http://dx.doi.org/10.1186/1471-2407-11-116] [PMID: 21453492]
[http://dx.doi.org/10.1016/j.jmb.2019.04.026] [PMID: 31034889]
[http://dx.doi.org/10.2174/1381612033454847] [PMID: 12769737]
[http://dx.doi.org/10.1039/C6OB01815G] [PMID: 27722734]
[http://dx.doi.org/10.3389/fphar.2019.01450] [PMID: 31920645]
[http://dx.doi.org/10.2174/138920012798356934] [PMID: 21892917]
[http://dx.doi.org/10.4155/fmc.14.125] [PMID: 25407370]
[http://dx.doi.org/10.1080/14686996.2019.1590126] [PMID: 31068982]
[http://dx.doi.org/10.1016/j.steroids.2018.12.003] [PMID: 30543816]
[http://dx.doi.org/10.1038/nrm3383] [PMID: 22722607]
[http://dx.doi.org/10.1016/j.ejcb.2005.08.010] [PMID: 16373174]
[http://dx.doi.org/10.1039/C5SC04392A] [PMID: 28660018]
[http://dx.doi.org/10.1021/acs.jmedchem.9b00634] [PMID: 31276399]
[http://dx.doi.org/10.1080/10495398.2012.760469] [PMID: 23534959]
[http://dx.doi.org/10.1080/17460441.2021.1942837] [PMID: 34187273]
[http://dx.doi.org/10.1016/j.bbamem.2016.09.021] [PMID: 27693190]
[http://dx.doi.org/10.2174/092986712799945003] [PMID: 22376031]
[http://dx.doi.org/10.1021/bi00124a018] [PMID: 1547240]
[http://dx.doi.org/10.1016/j.bbamem.2011.07.009] [PMID: 21819967]
[http://dx.doi.org/10.1021/acs.chemrev.6b00750] [PMID: 29292991]
[http://dx.doi.org/10.4155/fmc.12.75] [PMID: 22917248]
[http://dx.doi.org/10.1002/anie.201205674] [PMID: 23161799]
[http://dx.doi.org/10.1021/acs.orglett.6b01158] [PMID: 27194202]
[http://dx.doi.org/10.1021/acs.orglett.7b01742] [PMID: 28799768]
[http://dx.doi.org/10.3389/fnins.2017.00073] [PMID: 28261050]
[http://dx.doi.org/10.1016/j.coph.2019.01.003] [PMID: 30771730]
[http://dx.doi.org/10.1208/s12248-008-9071-2] [PMID: 19125334]
[http://dx.doi.org/10.3390/ph5090991] [PMID: 24280701]
[http://dx.doi.org/10.1023/A:1012188014919] [PMID: 9453065]
[http://dx.doi.org/10.1074/jbc.M110.198267] [PMID: 21518765]
[http://dx.doi.org/10.1016/j.jconrel.2011.01.025] [PMID: 21281679]
[http://dx.doi.org/10.1016/j.jconrel.2018.04.016] [PMID: 29653223]
[http://dx.doi.org/10.1021/acschembio.9b00987] [PMID: 32045202]
[http://dx.doi.org/10.1080/2162402X.2020.1728871] [PMID: 32158621]
[http://dx.doi.org/10.1007/s00262-015-1660-1] [PMID: 25662406]
[http://dx.doi.org/10.1007/s00262-020-02498-8] [PMID: 32025848]
[http://dx.doi.org/10.1016/j.clim.2016.03.015] [PMID: 27072896]
[http://dx.doi.org/10.1097/CJI.0000000000000405] [PMID: 34874330]
[http://dx.doi.org/10.1002/adhm.202001974] [PMID: 33929786]
[PMID: 26664119]
[http://dx.doi.org/10.1007/s10989-018-9772-z]
[http://dx.doi.org/10.1002/smll.201900936] [PMID: 31074941]
[http://dx.doi.org/10.1021/ja00897a025]
[http://dx.doi.org/10.1016/j.bmc.2017.06.052] [PMID: 28720325]
[http://dx.doi.org/10.1016/j.addr.2016.06.002] [PMID: 27313077]
[http://dx.doi.org/10.1039/C8CS00573G] [PMID: 30418441]