Abstract
Applications of biomarkers have been proved in oncology screening, diagnosis, predicting response to treatment as well as monitoring the progress of the disease. Considering the crucial role played by them during different disease stages, it is extremely important to evaluate, validate, and assess them to incorporate them into routine clinical care. In this review, the role of few most promising and successfully used biomarkers in cancer detection, i.e. PD-L1, E-Cadherin, TP53, Exosomes, cfDNA, EGFR, mTOR with regard to their structure, mode of action, and reports signifying their pathological significance, are addressed. Also, an overview of some successfully used biomarkers for cancer medicine has been presented. The study also summarizes biomarker-driven personalized cancer therapy i.e., approved targets and indications, as per the US FDA. The review also highlights the increasingly prominent role of biomarkers in drug development at all stages, with particular reference to clinical trials. The increasing utility of biomarkers in clinical trials is clearly evident from the trend shown, wherein ~55 percent of all oncology clinical trials in 2019 were seen to involve biomarkers, as opposed to ~ 15 percent in 2001, which clearly proves the essence and applicability of biomarkers for synergizing clinical information with tumor progression. Still, there are significant challenges in the implementation of these possibilities with strong evidence in cost-- effective manner.
Keywords: Biomarkers, PD-L1, targeted therapy, clinical trials, p53, EGFR, e-cadherin.
Graphical Abstract
[http://dx.doi.org/10.3390/cancers2010190] [PMID: 24281040]
[http://dx.doi.org/10.1016/j.molonc.2012.01.010] [PMID: 22356776]
[http://dx.doi.org/10.1177/1758834009360519] [PMID: 21789130]
[http://dx.doi.org/10.1007/s00428-013-1533-y] [PMID: 24487788]
[http://dx.doi.org/10.1200/JCO.2011.38.3729] [PMID: 22042948]
[http://dx.doi.org/10.1016/j.jprot.2012.03.046] [PMID: 22498886]
[http://dx.doi.org/10.3389/fimmu.2019.02022] [PMID: 31507611]
[http://dx.doi.org/10.1084/jem.192.7.1027] [PMID: 11015443]
[http://dx.doi.org/10.1038/nm730] [PMID: 12091876]
[http://dx.doi.org/10.1186/s40425-019-0768-9] [PMID: 31655605]
[http://dx.doi.org/10.1158/1535-7163.MCT-14-0983] [PMID: 25695955]
[http://dx.doi.org/10.1080/2162402X.2017.1408747] [PMID: 29632720]
[http://dx.doi.org/10.1097/PAS.0000000000001077] [PMID: 29762141]
[http://dx.doi.org/10.3389/fimmu.2018.01774] [PMID: 30105035]
[http://dx.doi.org/10.1038/nrc3239] [PMID: 22437870]
[http://dx.doi.org/10.1186/s12957-016-0969-3] [PMID: 27514667]
[http://dx.doi.org/10.1038/nature13480] [PMID: 25079317]
[PMID: 26487950]
[http://dx.doi.org/10.1038/ni1443] [PMID: 17304234]
[http://dx.doi.org/10.1111/j.1749-6632.2010.05919.x] [PMID: 21276005]
[PMID: 32627031]
[http://dx.doi.org/10.1080/14737140.2017.1301207] [PMID: 28277834]
[http://dx.doi.org/10.1136/jclinpath-2017-204853] [PMID: 29097600]
[http://dx.doi.org/10.1158/1055-9965.EPI-18-0779] [PMID: 30487133]
[http://dx.doi.org/10.1016/j.critrevonc.2017.06.001] [PMID: 28693793]
[http://dx.doi.org/10.1146/annurev.immunol.26.021607.090331] [PMID: 18173375]
[http://dx.doi.org/10.1038/nm1517] [PMID: 17159987]
[http://dx.doi.org/10.1182/blood-2006-10-051482] [PMID: 17363736]
[http://dx.doi.org/10.1073/pnas.0931259100] [PMID: 12697896]
[http://dx.doi.org/10.1097/COC.0000000000000239] [PMID: 26558876]
[http://dx.doi.org/10.1016/j.immuni.2007.05.016] [PMID: 17629517]
[http://dx.doi.org/10.1038/s41392-018-0022-9] [PMID: 30275987]
[http://dx.doi.org/10.5812/ircmj.4032] [PMID: 23984001]
[http://dx.doi.org/10.1016/j.febslet.2012.07.045] [PMID: 22841718]
[http://dx.doi.org/10.1101/2020.03.17.996181]
[http://dx.doi.org/10.3748/wjg.v12.i2.199] [PMID: 16482618]
[http://dx.doi.org/10.1200/JCO.2012.44.4612] [PMID: 23341533]
[http://dx.doi.org/10.1038/380360a0] [PMID: 8598933]
[http://dx.doi.org/10.3748/wjg.v12.i2.192] [PMID: 16482617]
[http://dx.doi.org/10.1016/j.yexcr.2005.07.010] [PMID: 16112667]
[PMID: 23749888]
[http://dx.doi.org/10.1002/ijc.10690] [PMID: 12397640]
[http://dx.doi.org/10.1038/sj.onc.1204505] [PMID: 11439345]
[http://dx.doi.org/10.1093/ajcp/111.1.29] [PMID: 9894451]
[http://dx.doi.org/10.1038/bjc.1998.309] [PMID: 9667659]
[http://dx.doi.org/10.1023/B:CLIN.0000017204.38807.22] [PMID: 15065605]
[http://dx.doi.org/10.1002/ijc.25438] [PMID: 20473926]
[http://dx.doi.org/10.1016/j.jss.2011.11.009] [PMID: 22277332]
[http://dx.doi.org/10.3892/ol.2017.6063] [PMID: 28588719]
[http://dx.doi.org/10.3892/ol.2018.8627] [PMID: 29928384]
[http://dx.doi.org/10.1073/pnas.1431692100] [PMID: 12826609]
[http://dx.doi.org/10.1016/S1040-8428(99)00051-7] [PMID: 10714958]
[http://dx.doi.org/10.3402/pba.v3i0.22702] [PMID: 24124625]
[http://dx.doi.org/10.1158/1078-0432.CCR-17-0408] [PMID: 28572266]
[http://dx.doi.org/10.1016/j.ejca.2005.11.032] [PMID: 16644204]
[http://dx.doi.org/10.1158/1078-0432.CCR-05-1029] [PMID: 16489069]
[http://dx.doi.org/10.1155/2011/284584] [PMID: 21760703]
[http://dx.doi.org/10.1038/sj.bjc.6601537] [PMID: 14760384]
[http://dx.doi.org/10.1186/bcr1675] [PMID: 17504517]
[http://dx.doi.org/10.1093/jjco/hyp007] [PMID: 19304743]
[http://dx.doi.org/10.1038/modpathol.2016.39] [PMID: 26939876]
[http://dx.doi.org/10.1182/blood.V84.9.3148.3148] [PMID: 7949187]
[http://dx.doi.org/10.1002/humu.10174] [PMID: 12619115]
[http://dx.doi.org/10.1177/1947601912455199] [PMID: 23150757]
[http://dx.doi.org/10.1101/gad.12.18.2831] [PMID: 9744860]
[http://dx.doi.org/10.1038/sj.onc.1210280] [PMID: 17401423]
[http://dx.doi.org/10.1242/jcs.03293] [PMID: 17158908]
[http://dx.doi.org/10.1002/humu.20495] [PMID: 17311302]
[PMID: 3597417]
[http://dx.doi.org/10.1371/journal.pone.0092921] [PMID: 24705249]
[http://dx.doi.org/10.1002/cncr.31062] [PMID: 29112225]
[http://dx.doi.org/10.3402/jev.v5.31488] [PMID: 27576678]
[http://dx.doi.org/10.3390/cancers11070898] [PMID: 31252648]
[http://dx.doi.org/10.1016/j.omtn.2018.05.009] [PMID: 30195762]
[http://dx.doi.org/10.1016/j.biopha.2019.108758] [PMID: 30877883]
[http://dx.doi.org/10.1515/cclm-2019-0052] [PMID: 30978169]
[http://dx.doi.org/10.1038/srep33935] [PMID: 27659060]
[http://dx.doi.org/10.1007/s13273-018-0014-4]
[http://dx.doi.org/10.1038/ncomms15016] [PMID: 28393839]
[http://dx.doi.org/10.1016/j.ccell.2014.09.005] [PMID: 25446899]
[http://dx.doi.org/10.1038/nature15376] [PMID: 26479035]
[http://dx.doi.org/10.1038/ncb3094] [PMID: 25621950]
[http://dx.doi.org/10.7150/ijbs.15514] [PMID: 27994512]
[http://dx.doi.org/10.7150/ijbs.27796]
[http://dx.doi.org/10.1038/215975b0] [PMID: 4964238]
[http://dx.doi.org/10.1126/science.148.3668.374]
[http://dx.doi.org/10.1186/s12867-017-0098-8] [PMID: 28793862]
[http://dx.doi.org/10.1007/s12038-015-9508-6] [PMID: 25740145]
[http://dx.doi.org/10.1158/0008-5472.CAN-12-3287] [PMID: 23722544]
[http://dx.doi.org/10.1371/journal.pone.0052754] [PMID: 23285175]
[PMID: 837366]
[http://dx.doi.org/10.1038/nm.3519] [PMID: 24705333]
[http://dx.doi.org/10.1126/scitranslmed.3007094] [PMID: 24553385]
[http://dx.doi.org/10.1038/nm.3564] [PMID: 24804754]
[http://dx.doi.org/10.1038/srep40737] [PMID: 28102343]
[http://dx.doi.org/10.1093/abbs/gmy104]
[http://dx.doi.org/10.1371/journal.pone.0131699] [PMID: 26133168]
[http://dx.doi.org/10.1134/S1990750812010052]
[http://dx.doi.org/10.7326/M15-0971] [PMID: 26756902]
[http://dx.doi.org/10.1056/NEJMoa1102873] [PMID: 21714641]
[http://dx.doi.org/10.1016/j.cell.2017.01.030] [PMID: 28187279]
[http://dx.doi.org/10.1126/science.aar3247]
[http://dx.doi.org/10.1186/s12916-016-0667-6] [PMID: 27558279]
[http://dx.doi.org/10.1126/scitranslmed.3004952] [PMID: 23303603]
[http://dx.doi.org/10.1056/NEJMoa1701717] [PMID: 28792880]
[http://dx.doi.org/10.1001/jamaoncol.2015.1883] [PMID: 26355862]
[http://dx.doi.org/10.1073/pnas.1508736112] [PMID: 26392541]
[http://dx.doi.org/10.1158/0008-5472.CAN-05-4556] [PMID: 16818665]
[PMID: 8137272]
[http://dx.doi.org/10.1016/j.bdq.2019.100087]
[http://dx.doi.org/10.1016/S0169-5002(03)00137-5] [PMID: 12867060]
[http://dx.doi.org/10.1001/jama.290.16.2149] [PMID: 14570950]
[http://dx.doi.org/10.1200/JCO.2004.11.057] [PMID: 15310767]
[http://dx.doi.org/10.1056/NEJMoa033025] [PMID: 15269313]
[http://dx.doi.org/10.1056/NEJMoa053422] [PMID: 16467544]
[http://dx.doi.org/10.1056/NEJMoa050736] [PMID: 16014883]
[http://dx.doi.org/10.1200/JCO.2005.01.2823] [PMID: 15998906]
[http://dx.doi.org/10.1093/jnci/dji112] [PMID: 15870435]
[http://dx.doi.org/10.1056/NEJMoa040938] [PMID: 15118073]
[http://dx.doi.org/10.1126/science.1099314] [PMID: 15118125]
[PMID: 2925616]
[PMID: 1988448]
[http://dx.doi.org/10.1002/14651858.CD010383.pub2] [PMID: 27223332]
[http://dx.doi.org/10.1016/j.jtho.2016.05.008] [PMID: 27229180]
[http://dx.doi.org/10.1038/nrc1609] [PMID: 15864276]
[http://dx.doi.org/10.1097/MPA.0000000000000389] [PMID: 26355547]
[http://dx.doi.org/10.1016/j.ctrv.2011.12.004] [PMID: 22226241]
[http://dx.doi.org/10.1097/00004347-199701000-00010] [PMID: 8986534]
[http://dx.doi.org/10.1155/2010/568938] [PMID: 20037743]
[http://dx.doi.org/10.3892/etm.2012.518] [PMID: 22969995]
[http://dx.doi.org/10.1002/cncr.26661] [PMID: 22086503]
[http://dx.doi.org/10.1097/PGP.0000000000000081] [PMID: 24901400]
[http://dx.doi.org/10.1038/sj.bjc.6604471] [PMID: 18628764]
[http://dx.doi.org/10.1002/cncr.22195] [PMID: 16983702]
[http://dx.doi.org/10.7314/APJCP.2014.15.22.9739] [PMID: 25520097]
[http://dx.doi.org/10.3892/etm.2012.481] [PMID: 22969977]
[http://dx.doi.org/10.1007/s11523-015-0369-6] [PMID: 26004768]
[http://dx.doi.org/10.1158/1078-0432.CCR-11-0408] [PMID: 22016507]
[http://dx.doi.org/10.1016/j.anndiagpath.2010.05.005] [PMID: 21074685]
[http://dx.doi.org/10.1186/1471-2407-11-294] [PMID: 21756326]
[http://dx.doi.org/10.2174/156800961509151110143001] [PMID: 26567882]
[http://dx.doi.org/10.1016/j.ejca.2014.07.001] [PMID: 25091798]
[http://dx.doi.org/10.1093/annonc/mdx304]
[http://dx.doi.org/10.1200/JCO.2005.04.8306] [PMID: 16763281]
[http://dx.doi.org/10.1016/j.ejca.2013.12.018] [PMID: 24424107]
[http://dx.doi.org/10.1038/nature14129] [PMID: 25631445]
[http://dx.doi.org/10.4161/cbt.20991] [PMID: 22825335]
[http://dx.doi.org/10.1016/S0959-8049(01)00231-3] [PMID: 11597399]
[http://dx.doi.org/10.1016/j.cell.2012.03.017] [PMID: 22500797]
[http://dx.doi.org/10.1016/j.cell.2017.03.035] [PMID: 28388417]
[http://dx.doi.org/10.2967/jnumed.111.089623] [PMID: 21421716]
[http://dx.doi.org/10.1093/nar/gkq929] [PMID: 20952405]
[http://dx.doi.org/10.2174/156800910791517172] [PMID: 20384580]
[http://dx.doi.org/10.1146/annurev-med-062913-051343] [PMID: 26473415]
[http://dx.doi.org/10.1158/2159-8290.CD-13-0063] [PMID: 24265156]
[http://dx.doi.org/10.1371/journal.pone.0116771] [PMID: 25680114]
[http://dx.doi.org/10.4161/cbt.7.9.6416] [PMID: 18708754]
[http://dx.doi.org/10.1016/j.canlet.2010.04.015] [PMID: 20471160]
[http://dx.doi.org/10.1016/j.ccr.2010.05.026] [PMID: 20579941]
[http://dx.doi.org/10.1038/sj.bjc.6605554] [PMID: 20104229]
[http://dx.doi.org/10.2174/156800909787580999] [PMID: 19275762]
[http://dx.doi.org/10.1186/s13578-020-00396-1] [PMID: 32175074]
[http://dx.doi.org/10.1126/sciadv.aar3938] [PMID: 30258985]
[http://dx.doi.org/10.1038/cr.2015.133] [PMID: 26584640]
[http://dx.doi.org/10.1038/ncb1183] [PMID: 15467718]
[http://dx.doi.org/10.1074/jbc.M114.627794] [PMID: 25882841]
[http://dx.doi.org/10.1038/370527a0] [PMID: 8052307]
[http://dx.doi.org/10.1172/JCI86120] [PMID: 27482884]
[http://dx.doi.org/10.1186/s40164-018-0122-9] [PMID: 30534474]
[http://dx.doi.org/10.1186/s13045-018-0662-9] [PMID: 30219074]
[http://dx.doi.org/10.1158/1078-0432.CCR-06-1503] [PMID: 17289895]
[http://dx.doi.org/10.1634/theoncologist.12-2-142] [PMID: 17296808]
[http://dx.doi.org/10.1200/JCO.2005.05.3934] [PMID: 16782929]
[http://dx.doi.org/10.1515/CCLM.2009.009] [PMID: 19055471]
[http://dx.doi.org/10.1016/S0002-9440(10)64592-0] [PMID: 10980118]
[http://dx.doi.org/10.1158/1078-0432.CCR-08-0186] [PMID: 18698037]
[http://dx.doi.org/10.1158/1078-0432.CCR-07-0408] [PMID: 17634537]
[http://dx.doi.org/10.1093/carcin/bgn086] [PMID: 18375955]
[http://dx.doi.org/10.1093/jnci/djk020] [PMID: 17228000]
[http://dx.doi.org/10.1200/JCO.2007.14.8924] [PMID: 18626007]
[PMID: 12133547]
[http://dx.doi.org/10.1093/annonc/mdl016] [PMID: 16497822]
[http://dx.doi.org/10.1056/NEJMoa065411] [PMID: 17314339]
[http://dx.doi.org/10.1016/j.ejca.2008.03.006] [PMID: 18396036]
[http://dx.doi.org/10.1056/NEJMoa1112302] [PMID: 22356324]
[PMID: 24534473]