Abstract
Background: Disease-modifying therapy in cancer can be defined as long-term treatment that has a beneficial outcome on the course of cancer, affecting the underlying pathophysiology of cancer. The anticancer potential of polyphenols is widely studied. However, there is a significant gap between experimental data obtained in vitro and in vitro and the current role of polyphenols in cancer therapy.
Objective: In this article, the reason for this inconsistency is discussed, which might be in the design of polyphenols clinical trials. The approach of long-term polyphenol disease-modifying therapy in cancer is encouraged.
Conclusion: The physiologic concentrations of polyphenols are not sufficient for reaching cytotoxic levels. Therefore, the immune modulation and effects on cancer signal transduction pathways should be considered in the design of polyphenol clinical trials. Such effects apparently can not cause the rapid regression of the disease. However, more likely, they can modulate the course of the disease, leading to favorable changes in the patient's condition in case of long-term treatment..
Keywords: polyphenols, flavonoids, cancer, disease-modifying therapy, inflammation, polyphenol trials.
Graphical Abstract
[http://dx.doi.org/10.3322/caac.21660] [PMID: 33538338]
[http://dx.doi.org/10.4161/oxim.2.5.9498] [PMID: 20716914]
[http://dx.doi.org/10.3390/cancers12103064] [PMID: 33092262]
[http://dx.doi.org/10.3390/nu10101523] [PMID: 30336572]
[http://dx.doi.org/10.3390/nu12072010] [PMID: 32640737]
[http://dx.doi.org/10.1016/j.foodchem.2019.01.128] [PMID: 30797367]
[http://dx.doi.org/10.1111/ene.12883] [PMID: 26563094]
[http://dx.doi.org/10.17116/jnevro20171172222-30] [PMID: 28617358]
[http://dx.doi.org/10.1016/j.jalz.2008.12.003] [PMID: 19751920]
[http://dx.doi.org/10.3389/fmed.2019.00223] [PMID: 31681780]
[http://dx.doi.org/10.1038/s41467-020-17670-y] [PMID: 32732879]
[http://dx.doi.org/10.1155/2018/1264074] [PMID: 29850614]
[http://dx.doi.org/10.1186/s13008-015-0012-z] [PMID: 26464579]
[http://dx.doi.org/10.3389/fphar.2017.00234] [PMID: 28503148]
[PMID: 29791099]
[http://dx.doi.org/10.3389/fimmu.2020.01180] [PMID: 32676076]
[http://dx.doi.org/10.1016/j.jnutbio.2021.108634] [PMID: 33794330]
[PMID: 23156087]
[http://dx.doi.org/10.1186/s12935-015-0260-7] [PMID: 26549987]
[http://dx.doi.org/10.1371/journal.pone.0139147] [PMID: 26440517]
[http://dx.doi.org/10.1002/biof.1199] [PMID: 25650983]
[http://dx.doi.org/10.1155/2017/6293740] [PMID: 28744339]
[http://dx.doi.org/10.1016/j.immuni.2019.06.025] [PMID: 31315034]
[http://dx.doi.org/10.1038/s41598-020-73624-w] [PMID: 33024179]
[http://dx.doi.org/10.1038/s41598-021-86514-6] [PMID: 33782464]
[http://dx.doi.org/10.1080/08923973.2018.1469145] [PMID: 30111198]
[http://dx.doi.org/10.3389/fonc.2015.00024] [PMID: 25763354]
[http://dx.doi.org/10.3390/ijms20184567] [PMID: 31540128]
[http://dx.doi.org/10.3389/fgene.2019.01150] [PMID: 31803237]
[http://dx.doi.org/10.3390/genes8060148] [PMID: 28545252]
[http://dx.doi.org/10.1002/jcb.29147] [PMID: 31172592]
[http://dx.doi.org/10.3389/fgene.2019.00514] [PMID: 31214247]
[PMID: 30655872]
[http://dx.doi.org/10.1016/j.jhep.2015.04.018] [PMID: 25937435]
[http://dx.doi.org/10.1038/s41598-020-62136-2] [PMID: 32198390]
[http://dx.doi.org/10.3892/ijfn.2020.9]
[http://dx.doi.org/10.1016/j.semcancer.2016.09.001] [PMID: 27609747]
[http://dx.doi.org/10.3892/ijo.2014.2379] [PMID: 24728148]
[http://dx.doi.org/10.1016/j.canlet.2012.05.029] [PMID: 22659736]
[http://dx.doi.org/10.1155/2015/878134] [PMID: 25879038]
[http://dx.doi.org/10.1093/carcin/bgy076] [PMID: 29860383]
[http://dx.doi.org/10.21037/atm-20-3329] [PMID: 32566617]
[http://dx.doi.org/10.1158/1535-7163.MCT-18-0464] [PMID: 30404927]
[http://dx.doi.org/10.1053/j.gastro.2015.07.058] [PMID: 26255562]
[http://dx.doi.org/10.3389/fonc.2020.574827] [PMID: 33552955]
[http://dx.doi.org/10.1021/acs.molpharmaceut.7b00545] [PMID: 28870081]
[PMID: 30783443]
[http://dx.doi.org/10.1038/s41598-018-23840-2] [PMID: 29686295]
[http://dx.doi.org/10.1093/gastro/goaa072] [PMID: 33747527]
[http://dx.doi.org/10.1016/j.phrs.2011.05.007] [PMID: 21624470]
[http://dx.doi.org/10.1158/1940-6207.CAPR-16-0167] [PMID: 28325826]
[http://dx.doi.org/10.1093/jn/138.9.1615] [PMID: 18716159]
[http://dx.doi.org/10.1073/pnas.1901659116] [PMID: 31036637]
[http://dx.doi.org/10.1158/1078-0432.CCR-04-0744] [PMID: 15501961]
[http://dx.doi.org/10.1186/s12885-020-07256-8] [PMID: 32838749]
[http://dx.doi.org/10.3389/fnut.2018.00025] [PMID: 29713632]
[http://dx.doi.org/10.1177/039463201302600111] [PMID: 23527714]
[http://dx.doi.org/10.3390/ijms20071714] [PMID: 30959898]
[http://dx.doi.org/10.1002/pros.23766] [PMID: 30671976]
[http://dx.doi.org/10.1158/1940-6207.CAPR-11-0306] [PMID: 22044694]
[http://dx.doi.org/10.1016/j.fct.2020.111260] [PMID: 32179165]
[http://dx.doi.org/10.3322/caac.21632] [PMID: 32964460]
[http://dx.doi.org/10.21873/invivo.11791] [PMID: 31882509]
[http://dx.doi.org/10.1158/1940-6207.CAPR-16-0209] [PMID: 27913448]
[http://dx.doi.org/10.1016/j.jcis.2019.01.103] [PMID: 30710823]
[http://dx.doi.org/10.1016/j.colsurfb.2018.11.068] [PMID: 30517904]
[http://dx.doi.org/10.1126/scirobotics.aaz9519] [PMID: 34043546]
[http://dx.doi.org/10.1016/j.jconrel.2021.10.025] [PMID: 34695523]
[http://dx.doi.org/10.2147/IJN.S132434] [PMID: 28860764]
[http://dx.doi.org/10.15171/apb.2017.005] [PMID: 28507935]
[http://dx.doi.org/10.1016/j.phrs.2018.03.013] [PMID: 29614381]
[http://dx.doi.org/10.3389/fonc.2021.612903] [PMID: 33767985]
[http://dx.doi.org/10.1016/j.phymed.2020.153218] [PMID: 32335356]