Skip to content
2000
  1. Home
  2. A-Z Publications
  3. Current Reviews in Clinical and Experimental Pharmacology
  4. Volume 20, Issue 2
  5. Article
Volume 20, Issue 2
  • ISSN: 2772-4328
  • E-ISSN: 2772-4336

Abstract

Cancer is a high-morbidity disease prevalent worldwide. Chemotherapy is the primarily used regimen for cancer treatment; however, it also brings severe side effects. Chemotherapy-induced Peripheral Neuropathy (CIPN) and Chemotherapy-induced Cognitive Impairment (CICI) are two main complications occurring in chemotherapy. They are both associated with nervous system injury and are therefore collectively referred to as Chemotherapy-induced Neuropathy (CIN). CIPN induces neuralgia and numbness in limbs, while CICI causes amnesia and cognitive dysfunction. Currently, there are no effective therapeutics to prevent or cure CIN, so research into new drugs to alleviate CIN becomes urgent. Oxidative stress and neuroinflammation are the common pathogenic mechanisms of CIPN and CICI. Excessive Reactive Oxygen Species (ROS) and pro-inflammatory cytokines cause peripheral nervous system damage and hence CIPN. Peripheral ROS and cytokines also change the permeability of the blood-brain barrier, thereby increasing oxidative stress and neuroinflammation in the central nervous system, ultimately leading to CICI. Several antidepressants have been used to treat CIN and exhibited good clinical effects. Their potential pharmacological mechanism has been reported to ameliorate oxidative stress and neuroinflammation, guiding a new feasible way for effective therapeutic development against CIN. This mini-review has summarized the latest advances in the research on CIN with respect to clinical status, pathogenesis, and treatment. It has also discussed the potential of repurposing antidepressants for CIN treatment and prospected the strategy of developing therapeutics by targeting oxidative stress and neuroinflammation against CIN.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/crcep/10.2174/0127724328314214240829181006
2024-09-10
2025-05-11

  • From This Site

    /content/journals/crcep/10.2174/0127724328314214240829181006
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. SungH. FerlayJ. SiegelR.L. LaversanneM. SoerjomataramI. JemalA. BrayF. Global cancer statistics 2020: Globocan estimates of incidence and mortality worldwide for 36 cancers in 185 countries.CA Cancer J. Clin.202171320924910.3322/caac.2166033538338
     [Google Scholar]
  2. FerlayJ. ColombetM. SoerjomataramI. ParkinD.M. PiñerosM. ZnaorA. BrayF. Cancer statistics for the year 2020: An overview.Int. J. Cancer2021149477878910.1002/ijc.3358833818764
     [Google Scholar]
  3. SeetharamanP.K. ChandrasekaranR. PeriakaruppanR. GnanasekarS. SivaperumalS. Abd-ElsalamK.A. ValisM. KucaK. Functional attributes of myco-synthesized silver nanoparticles from endophytic fungi: A new implication in biomedical applications.Biology (Basel)202110647310.3390/biology1006047334071886
     [Google Scholar]
  4. ZengH. ChenW. ZhengR. ZhangS. JiJ.S. ZouX. XiaC. SunK. YangZ. LiH. WangN. HanR. LiuS. LiH. MuH. HeY. XuY. FuZ. ZhouY. JiangJ. YangY. ChenJ. WeiK. FanD. WangJ. FuF. ZhaoD. SongG. ChenJ. JiangC. ZhouX. GuX. JinF. LiQ. LiY. WuT. YanC. DongJ. HuaZ. BaadeP. BrayF. JemalA. YuX.Q. HeJ. Changing cancer survival in China during 2003–15: A pooled analysis of 17 population-based cancer registries.Lancet Glob. Health201865e555e56710.1016/S2214‑109X(18)30127‑X29653628
     [Google Scholar]
  5. JiangZ.G. FullerS.A. GhanbariH.A. PAN-811 blocks chemotherapy drug-induced in vitro neurotoxicity, while not affecting suppression of cancer cell growth.Oxid. Med. Cell. Longev.2016201611110.1155/2016/939240426640619
     [Google Scholar]
  6. SeretnyM. CurrieG.L. SenaE.S. RamnarineS. GrantR. MacLeodM.R. ColvinL.A. FallonM. Incidence, prevalence, and predictors of chemotherapy-induced peripheral neuropathy: A systematic review and meta-analysis.Pain2014155122461247010.1016/j.pain.2014.09.02025261162
     [Google Scholar]
  7. BurgessJ. FerdousiM. GosalD. BoonC. MatsumotoK. MarshallA. MakT. MarshallA. FrankB. MalikR.A. AlamU. Chemotherapy-induced peripheral neuropathy: Epidemiology, pathomechanisms and treatment.Oncol. Ther.20219238545010.1007/s40487‑021‑00168‑y34655433
     [Google Scholar]
  8. TengC. CohenJ. EggerS. BlinmanP.L. VardyJ.L. Systematic review of long-term chemotherapy-induced peripheral neuropathy (CIPN) following adjuvant oxaliplatin for colorectal cancer.Support. Care Cancer2022301334710.1007/s00520‑021‑06502‑434410459
     [Google Scholar]
  9. DasA. RanadiveN. KinraM. NampoothiriM. AroraD. MudgalJ. An overview on chemotherapy-induced cognitive impairment and potential role of antidepressants.Curr. Neuropharmacol.202018983885110.2174/1570159X1866620022111384232091339
     [Google Scholar]
  10. BrewerJ.R. MorrisonG. DolanM.E. FlemingG.F. Chemotherapy-induced peripheral neuropathy: Current status and progress.Gynecol. Oncol.2016140117618310.1016/j.ygyno.2015.11.01126556766
     [Google Scholar]
  11. ZajączkowskaR. Kocot-KępskaM. LeppertW. WrzosekA. MikaJ. WordliczekJ. Mechanisms of chemotherapy-induced peripheral neuropathy.Int. J. Mol. Sci.2019206145110.3390/ijms2006145130909387
     [Google Scholar]
  12. BanachM. JuranekJ.K. ZygulskaA.L. Chemotherapy-induced neuropathies—a growing problem for patients and health care providers.Brain Behav.201771e0055810.1002/brb3.55828127506
     [Google Scholar]
  13. AretiA. YerraV.G. NaiduV.G.M. KumarA. Oxidative stress and nerve damage: Role in chemotherapy induced peripheral neuropathy.Redox Biol.2014228929510.1016/j.redox.2014.01.00624494204
     [Google Scholar]
  14. Zaks-ZilbermanM. ZaksT.Z. VogelS.N. Induction of proinflammatory and chemokine genes by lipopolysaccharide and paclitaxel (taxol™) in murine and human breast cancer cell lines.Cytokine200115315616510.1006/cyto.2001.093511554785
     [Google Scholar]
  15. MounierN.M. Abdel-MagedA.E.S. WahdanS.A. GadA.M. AzabS.S. Chemotherapy-induced cognitive impairment (CICI): An overview of etiology and pathogenesis.Life Sci.202025811807110.1016/j.lfs.2020.11807132673664
     [Google Scholar]
  16. AluiseC.D. MiriyalaS. NoelT. SultanaR. JungsuwadeeP. TaylorT.J. CaiJ. PierceW.M. VoreM. MoscowJ.A. St ClairD.K. ButterfieldD.A. 2-Mercaptoethane sulfonate prevents doxorubicin-induced plasma protein oxidation and TNF-α release: Implications for the reactive oxygen species-mediated mechanisms of chemobrain.Free Radic. Biol. Med.201150111630163810.1016/j.freeradbiomed.2011.03.00921421044
     [Google Scholar]
  17. RummelN.G. ChaiswingL. BondadaS. St ClairD.K. ButterfieldD.A. Chemotherapy-induced cognitive impairment: Focus on the intersection of oxidative stress and TNFα.Cell. Mol. Life Sci.20217819-206533654010.1007/s00018‑021‑03925‑434424346
     [Google Scholar]
  18. KeeneyJ.T.R. RenX. WarrierG. NoelT. PowellD.K. BrelsfoardJ.M. SultanaR. SaatmanK.E. ClairD.K.S. ButterfieldD.A. Doxorubicin-induced elevated oxidative stress and neurochemical alterations in brain and cognitive decline: Protection by MESNA and insights into mechanisms of chemotherapy-induced cognitive impairment (“chemobrain”).Oncotarget2018954303243033910.18632/oncotarget.2571830100992
     [Google Scholar]
  19. CummingsJ. AndersonL. WillmottN. SmythJ.F. The molecular pharmacology of doxorubicin in vivo.Eur. J. Cancer Clin. Oncol.199127553253510.1016/0277‑5379(91)90209‑V1647181
     [Google Scholar]
  20. AlhowailA.H. BloemerJ. MajrashiM. PinkyP.D. BhattacharyaS. YongliZ. BhattacharyaD. EggertM. WoodieL. BuabeidM.A. JohnsonN. BroadwaterA. SmithB. DhanasekaranM. ArnoldR.D. SuppiramaniamV. Doxorubicin-induced neurotoxicity is associated with acute alterations in synaptic plasticity, apoptosis, and lipid peroxidation.Toxicol. Mech. Methods201929645746610.1080/15376516.2019.160008631010378
     [Google Scholar]
  21. BrandoliniL. d’AngeloM. AntonosanteA. CiminiA. AllegrettiM. Chemokine signaling in chemotherapy-induced neuropathic pain.Int. J. Mol. Sci.20192012290410.3390/ijms2012290431197114
     [Google Scholar]
  22. StaffN.P. GrisoldA. GrisoldW. WindebankA.J. Chemotherapy-induced peripheral neuropathy: A current review.Ann. Neurol.201781677278110.1002/ana.2495128486769
     [Google Scholar]
  23. BrancaJ.J.V. MarescaM. MorucciG. BecattiM. PaternostroF. GulisanoM. GhelardiniC. SalveminiD. Di Cesare MannelliL. PaciniA. Oxaliplatin-induced blood brain barrier loosening: A new point of view on chemotherapy-induced neurotoxicity.Oncotarget2018934234262343810.18632/oncotarget.2519329805744
     [Google Scholar]
  24. WangC. ZhaoY. WangL. PanS. LiuY. LiS. WangD. C-phycocyanin mitigates cognitive impairment in doxorubicin-Induced chemobrain: Impact on neuroinflammation, oxidative stress, and brain mitochondrial and synaptic alterations.Neurochem. Res.202146214915810.1007/s11064‑020‑03164‑233237471
     [Google Scholar]
  25. TongY. WangK. ShengS. CuiJ. Polydatin ameliorates chemotherapy-induced cognitive impairment (chemobrain) by inhibiting oxidative stress, inflammatory response, and apoptosis in rats.Biosci. Biotechnol. Biochem.20208461201121010.1080/09168451.2020.172205731992173
     [Google Scholar]
  26. BattagliniE. ParkS.B. BarnesE.H. GoldsteinD. A double blind, placebo controlled, phase II randomised cross-over trial investigating the use of duloxetine for the treatment of chemotherapy-induced peripheral neuropathy.Contemp. Clin. Trials20187013513810.1016/j.cct.2018.04.01129680317
     [Google Scholar]
  27. LiuD. WangZ. LiuS. WangF. ZhaoS. HaoA. Anti-inflammatory effects of fluoxetine in lipopolysaccharide(LPS)-stimulated microglial cells.Neuropharmacology201161459259910.1016/j.neuropharm.2011.04.03321575647
     [Google Scholar]
  28. WalkerF.R. A critical review of the mechanism of action for the selective serotonin reuptake inhibitors: Do these drugs possess anti-inflammatory properties and how relevant is this in the treatment of depression?Neuropharmacology20136730431710.1016/j.neuropharm.2012.10.00223085335
     [Google Scholar]
  29. BehrG.A. MoreiraJ.C.F. FreyB.N. Preclinical and clinical evidence of antioxidant effects of antidepressant agents: Implications for the pathophysiology of major depressive disorder.Oxid. Med. Cell. Longev.2012201211310.1155/2012/60942122693652
     [Google Scholar]
  30. Arteaga-HenríquezG. SimonM.S. BurgerB. WeidingerE. WijkhuijsA. AroltV. BirkenhagerT.K. MusilR. MüllerN. DrexhageH.A. Low-grade inflammation as a predictor of antidepressant and anti-inflammatory therapy response in MDD patients: A systematic review of the literature in combination with an analysis of experimental data collected in the EU-MOODINFLAME consortium.Front. Psychiatry20191045810.3389/fpsyt.2019.0045831354538
     [Google Scholar]
/content/journals/crcep/10.2174/0127724328314214240829181006
Loading
Insights into the Pathogenesis and Treatment of Chemotherapy-Induced Neuropathy: A Focus on Oxidative Stress and Neuroinflammation
Curr Rev Clin Exper Pharm 20, 98 (2025); https://doi.org/10.2174/0127724328314214240829181006
/content/journals/crcep/10.2174/0127724328314214240829181006
/content/journals/crcep/10.2174/0127724328314214240829181006
Loading

Data & Media loading...


  • Article Type:     Review Article
Keyword(s): cancer treatment; CICI; CIN; CIPN; neuroinflammation; oxidative stress

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test