Abstract
Therapy-induced tumor resistance has always been a paramount hurdle in the clinical triumph of cancer therapy. Resistance acquired by tumor through interventions of chemotherapeutic drugs, ionizing radiation, and immunotherapy in the patients is a severe drawback and major cause of recurrence of tumor and failure of therapeutic responses. To counter acquired resistance in tumor cells, several strategies are practiced such as chemotherapy regimens, immunotherapy and immunoconjugates, but the outcome is very disappointing for the patients as well as clinicians.
Radionuclide therapy using alpha or beta-emitting radionuclide as payload becoming a popular practice for cancer therapy. With the improvement in dosimetric studies, development of high-affinity target molecules and design of several novel chelating agents which provide thermodynamically stable complexes in vivo, the scope of radionuclide therapy has increased by leaps and bounds. Additionally, radionuclide therapy along with the combination of chemotherapy is gaining importance in pre-clinics, which is quite encouraging. Thus, it opens an avenue for newer cancer therapy modalities where chemotherapy, radiation therapy, and immunotherapy are unable to break the silence of tumor response. This article describes, in brief, the causes of tumor resistance and discusses the potential of radionuclide therapy to enhance tumor response.
Keywords: Cancer therapy, nuclear medicine, radiation therapy, radiopharmaceuticals, targeted radionuclide therapy, combination therapy.
Graphical Abstract
[http://dx.doi.org/10.3390/cancers8030032] [PMID: 26959063]
[http://dx.doi.org/10.15171/apb.2017.041] [PMID: 29071215]
[http://dx.doi.org/10.1152/ajplegacy.1940.128.3.565]
[http://dx.doi.org/10.1038/256495a0] [PMID: 1172191]
[PMID: 22180677]
[http://dx.doi.org/10.1038/248704a0] [PMID: 4833275]
[http://dx.doi.org/10.3389/fmed.2016.00005] [PMID: 26942181]
[http://dx.doi.org/10.1097/HP.0000000000001000] [PMID: 30585960]
[http://dx.doi.org/10.3390/ph12010002] [PMID: 30586898]
[http://dx.doi.org/10.1038/emm.2017.35] [PMID: 28336959]
[http://dx.doi.org/10.1007/s002800051053] [PMID: 9272126]
[http://dx.doi.org/10.3390/molecules22010006] [PMID: 28025535]
[http://dx.doi.org/10.1016/j.biomaterials.2016.11.013] [PMID: 27886555]
[http://dx.doi.org/10.1080/15216540701736285] [PMID: 18085475]
[http://dx.doi.org/10.18632/oncotarget.19048] [PMID: 28938696]
[http://dx.doi.org/10.1146/annurev.med.53.082901.103929] [PMID: 11818492]
[PMID: 17201178]
[http://dx.doi.org/10.1038/nrc3599] [PMID: 24060863]
[http://dx.doi.org/10.1177/147323001204000204] [PMID: 22613403]
[http://dx.doi.org/10.2174/187152013804487380] [PMID: 22931413]
[http://dx.doi.org/10.4236/pp.2015.63017]
[http://dx.doi.org/10.1038/s41575-019-0247-2] [PMID: 32005946]
[PMID: 2049898]
[http://dx.doi.org/10.1038/s41467-019-11906-2] [PMID: 31477729]
[http://dx.doi.org/10.1002/jlb.49.4.388] [PMID: 1900523]
[http://dx.doi.org/10.1111/j.1349-7006.2000.tb00906.x] [PMID: 11092988]
[http://dx.doi.org/10.1038/sj.onc.1208049] [PMID: 15326475]
[http://dx.doi.org/10.1158/0008-5472.CAN-04-3028] [PMID: 15930309]
[http://dx.doi.org/10.1126/science.1059108] [PMID: 11326099]
[PMID: 9815569]
[http://dx.doi.org/10.1016/S0360-3016(00)01558-3] [PMID: 11316541]
[http://dx.doi.org/10.1038/sj.bjc.6602647] [PMID: 15928664]
[http://dx.doi.org/10.1038/351453a0] [PMID: 2046748]
[http://dx.doi.org/10.1073/pnas.89.16.7491] [PMID: 1323840]
[http://dx.doi.org/10.1073/pnas.90.12.5742] [PMID: 8516323]
[PMID: 1423286]
[PMID: 10197600]
[http://dx.doi.org/10.1097/JTO.0b013e3181a1084f] [PMID: 19404218]
[http://dx.doi.org/10.1182/blood.V90.6.2188] [PMID: 9310469]
[http://dx.doi.org/10.4161/mabs.1.3.8292] [PMID: 20065642]
[http://dx.doi.org/10.1016/j.molimm.2015.04.002] [PMID: 25911943]
[http://dx.doi.org/10.3389/fonc.2018.00163] [PMID: 29915719]
[http://dx.doi.org/10.1016/j.beha.2011.02.009] [PMID: 21658619]
[http://dx.doi.org/10.1200/JCO.1998.16.8.2825] [PMID: 9704735]
[http://dx.doi.org/10.1200/JCO.2006.10.5437] [PMID: 17664471]
[http://dx.doi.org/10.18632/oncotarget.14012] [PMID: 28002810]
[http://dx.doi.org/10.1158/2159-8290.CD-12-0558] [PMID: 23729478]
[http://dx.doi.org/10.1038/s41598-019-51981-5] [PMID: 31653970]
[http://dx.doi.org/10.1056/NEJM200103153441101] [PMID: 11248153]
[http://dx.doi.org/10.1200/JCO.2002.20.3.719] [PMID: 11821453]
[http://dx.doi.org/10.1056/NEJMoa052122] [PMID: 16236738]
[http://dx.doi.org/10.1158/0008-5472-CAN-04-3913] [PMID: 15805248]
[http://dx.doi.org/10.1056/NEJMcibr043143] [PMID: 15564551]
[http://dx.doi.org/10.1158/0008-5472.CAN-07-5962] [PMID: 18316611]
[http://dx.doi.org/10.1002/cncr.10553] [PMID: 12115372]
[PMID: 21277939]
[http://dx.doi.org/10.1111/j.1349-7006.2010.01711.x] [PMID: 20825420]
[http://dx.doi.org/10.1586/era.10.226] [PMID: 21342044]
[http://dx.doi.org/10.1615/CritRevOncog.v17.i1.20] [PMID: 22471661]
[http://dx.doi.org/10.4161/cbt.11.9.15045] [PMID: 21307659]
[http://dx.doi.org/10.2174/092986712799320691] [PMID: 22229414]
[http://dx.doi.org/10.4161/cc.10.17.16359] [PMID: 21862872]
[http://dx.doi.org/10.1158/0008-5472.CAN-04-3841] [PMID: 16322262]
[http://dx.doi.org/10.1038/bjc.2014.72] [PMID: 24595002]
[http://dx.doi.org/10.1038/bjc.2012.85] [PMID: 22454081]
[http://dx.doi.org/10.3390/pharmaceutics13010049] [PMID: 33396374]
[http://dx.doi.org/10.1186/s41181-019-0075-2] [PMID: 31659527]
[http://dx.doi.org/10.1016/j.rpor.2014.08.004] [PMID: 25535579]
[http://dx.doi.org/10.1088/0031-9155/53/7/007] [PMID: 18364546]
[http://dx.doi.org/10.4137/BIC.S31804] [PMID: 27226737]
[http://dx.doi.org/10.1016/j.niox.2008.04.026] [PMID: 18503779]
[http://dx.doi.org/10.3389/fonc.2013.00177] [PMID: 23875170]
[http://dx.doi.org/10.4103/1450-1147.89780] [PMID: 22144871]
[http://dx.doi.org/10.2174/1874471007666140716115938] [PMID: 25030623]
[http://dx.doi.org/10.1016/S1470-2045(20)30323-5] [PMID: 32888472]
[http://dx.doi.org/10.3390/cancers12102916] [PMID: 33050580]
[http://dx.doi.org/10.1016/j.ejca.2013.04.008] [PMID: 23684782]
[http://dx.doi.org/10.1038/nrclinonc.2011.160] [PMID: 22064461]
[PMID: 16741311]
[http://dx.doi.org/10.2174/18744710113066660023] [PMID: 24059327]
[http://dx.doi.org/10.1517/17425247.2013.808184] [PMID: 23751126]
[http://dx.doi.org/10.1615/JEnvironPatholToxicolOncol.2013006843] [PMID: 24099423]
[http://dx.doi.org/10.1016/j.nucmedbio.2011.10.020] [PMID: 22172384]
[http://dx.doi.org/10.2147/OTT.S202867] [PMID: 32431509]
[http://dx.doi.org/10.1038/nrc3925] [PMID: 25998714]
[http://dx.doi.org/10.1080/17434440.2020.1796633] [PMID: 32669004]
[http://dx.doi.org/10.1038/sj.bmt.1705182] [PMID: 16247432]
[PMID: 16739341]
[http://dx.doi.org/10.1023/A:1011160913619] [PMID: 11521799]
[http://dx.doi.org/10.1007/s00259-011-1833-x] [PMID: 21553086]
[http://dx.doi.org/10.1007/s00259-014-2710-1] [PMID: 24570096]
[http://dx.doi.org/10.1007/s00259-020-04690-5] [PMID: 31980909]
[http://dx.doi.org/10.1053/j.semnuclmed.2015.12.003] [PMID: 27067503]
[http://dx.doi.org/10.1200/JCO.2018.78.5865] [PMID: 29878866]
[http://dx.doi.org/10.1016/S1470-2045(18)30198-0] [PMID: 29752180]
[http://dx.doi.org/10.1016/j.jvir.2016.01.147] [PMID: 27062356]
[http://dx.doi.org/10.2967/jnumed.116.184713] [PMID: 28082436]
[http://dx.doi.org/10.1148/radiol.11110361] [PMID: 22025735]
[http://dx.doi.org/10.1586/14737140.2.5.485] [PMID: 12382517]
[http://dx.doi.org/10.1200/JCO.2004.00.9217] [PMID: 16186600]
[http://dx.doi.org/10.1016/j.radonc.2020.11.013] [PMID: 33227356]
[http://dx.doi.org/10.1016/S1470-2045(19)30798-3] [PMID: 32014119]
[http://dx.doi.org/10.1002/ijc.30500] [PMID: 27813061]
[PMID: 12941838]
[http://dx.doi.org/10.1158/1535-7163.MCT-17-0554] [PMID: 29054987]
[http://dx.doi.org/10.2967/jnumed.112.115170] [PMID: 23572496]
[http://dx.doi.org/10.1200/JCO.2009.27.7863] [PMID: 20625137]
[http://dx.doi.org/10.1038/s41598-019-43880-6] [PMID: 31110198]
[http://dx.doi.org/10.1056/NEJMoa1213755] [PMID: 23863050]
[http://dx.doi.org/10.1200/JCO.1998.16.4.1574] [PMID: 9552068]
[PMID: 23976864]
[http://dx.doi.org/10.1021/cr3003104] [PMID: 23198879]
[http://dx.doi.org/10.1507/endocrj.K11E-051] [PMID: 21551958]
[http://dx.doi.org/10.3389/fmolb.2020.609172] [PMID: 33335914]
[http://dx.doi.org/10.2174/092986710791859315] [PMID: 20586723]
[http://dx.doi.org/10.1158/0008-5472.CAN-06-3569] [PMID: 17332322]
[http://dx.doi.org/10.18632/oncotarget.817] [PMID: 23474846]
[PMID: 15640792]
[http://dx.doi.org/10.1074/mcp.M800515-MCP200] [PMID: 19346216]
[http://dx.doi.org/10.4049/jimmunol.172.5.3280] [PMID: 14978136]
[http://dx.doi.org/10.1007/s00259-019-04340-5] [PMID: 31098749]
[http://dx.doi.org/10.1093/oxfordjournals.rpd.a006222] [PMID: 14526955]
[http://dx.doi.org/10.1093/oxfordjournals.rpd.a006318] [PMID: 14527040]
[http://dx.doi.org/10.1158/1078-0432.CCR-08-1403] [PMID: 19276251]
[http://dx.doi.org/10.3960/jslrt.56.89] [PMID: 27980307]
[http://dx.doi.org/10.1016/S1470-2045(05)70169-8] [PMID: 15863381]
[http://dx.doi.org/10.3109/09553002.2016.1144944] [PMID: 26917443]
[http://dx.doi.org/10.1016/j.biochi.2006.06.011] [PMID: 16996675]
[http://dx.doi.org/10.1097/00007611-197806000-00021] [PMID: 663699]
[http://dx.doi.org/10.2967/jnumed.119.227835] [PMID: 31519805]
[http://dx.doi.org/10.3390/biomedicines8110461] [PMID: 33142986]
[http://dx.doi.org/10.1634/theoncologist.2009-S104] [PMID: 20413641]
[http://dx.doi.org/10.1007/BF02234904]
[http://dx.doi.org/10.1016/j.mrgentox.2006.07.002] [PMID: 16973408]
[http://dx.doi.org/10.1016/j.tox.2006.09.004] [PMID: 17049709]
[http://dx.doi.org/10.1002/jbt.20228] [PMID: 18561333]
[http://dx.doi.org/10.1007/s11010-005-0170-4] [PMID: 16311925]
[http://dx.doi.org/10.1016/j.mrgentox.2005.11.002] [PMID: 16406783]
[http://dx.doi.org/10.2174/187152012803833026] [PMID: 22583408]
[http://dx.doi.org/10.1080/01635581.2010.509835] [PMID: 20924967]
[http://dx.doi.org/10.4103/0973-0168.199309]
[http://dx.doi.org/10.1016/j.bmc.2014.03.010] [PMID: 24702859]
[http://dx.doi.org/10.1039/C5RA15380H]
[http://dx.doi.org/10.1016/j.foodres.2015.07.027] [PMID: 28455046]
[http://dx.doi.org/10.25011/cim.v31i5.4870] [PMID: 18980713]
[http://dx.doi.org/10.1016/j.ejphar.2012.06.037] [PMID: 22771294]
[http://dx.doi.org/10.1016/j.jnutbio.2008.10.002] [PMID: 19157829]
[http://dx.doi.org/10.1016/j.tox.2009.05.004] [PMID: 19450652]
[http://dx.doi.org/10.1016/j.bbagen.2006.11.008] [PMID: 17189673]
[http://dx.doi.org/10.1007/s00411-019-00795-0] [PMID: 31123854]
[http://dx.doi.org/10.1177/147323001103900412] [PMID: 21986126]
[http://dx.doi.org/10.1002/ptr.3091] [PMID: 20041432]
[http://dx.doi.org/10.1080/01635580903285171] [PMID: 20155616]
[http://dx.doi.org/10.1002/jcb.22601] [PMID: 20564188]
[http://dx.doi.org/10.1196/annals.1397.047] [PMID: 17404056]
[http://dx.doi.org/10.1016/j.bbrc.2004.12.081] [PMID: 15649425]
[http://dx.doi.org/10.1016/B978-0-12-812373-7.00003-6]
[http://dx.doi.org/10.1111/j.1749-6632.2010.05852.x] [PMID: 21261654]
[http://dx.doi.org/10.1038/85798] [PMID: 11242102]
[http://dx.doi.org/10.1007/s00411-013-0499-0] [PMID: 24240273]
[http://dx.doi.org/10.14719/pst.2019.6.2.513]
[http://dx.doi.org/10.2174/1871520620666200424124746] [PMID: 32329694]
[http://dx.doi.org/10.4238/2014.March.31.5] [PMID: 24737473]
[http://dx.doi.org/10.2174/18744710113069990021] [PMID: 23895775]
[http://dx.doi.org/10.1089/cbr.2014.1663] [PMID: 25226352]
[http://dx.doi.org/10.2967/jnumed.120.248062] [PMID: 33037092]
[http://dx.doi.org/10.1016/S1470-2045(17)30379-0] [PMID: 28677577]
[http://dx.doi.org/10.7150/thno.39203] [PMID: 31695808]
[http://dx.doi.org/10.2967/jnumed.112.117952] [PMID: 23918734]
[http://dx.doi.org/10.3390/cancers12092721] [PMID: 32971984]
[http://dx.doi.org/10.1089/cbr.2018.2683] [PMID: 30977670]