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Current Pharmacogenomics and Personalized Medicine

Current Pharmacogenomics and Personalized Medicine

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ISSN (Print): 1875-6921
ISSN (Online): 1875-6913

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Review Article

Chemotherapy Drug-induced Neurotoxicity: A Pharmacogenomic Perspective

Author(s): Anisa Devi Kharisma Wibowoorcid of author, Muhammad Reza Mahendraorcid of author, Lalu Muhammad Irham*orcid of author, Wirawan Adikusumaorcid of author, Danang Prasetyaning Amuktiorcid of author, Maulida Mazayaorcid of author, Rockie Chongorcid of author, Rina Mutiaraorcid of author, Darmawi Darmawiorcid of author, Amelia Nur Vidyantiorcid of author and Ilker Ates

Volume 23, 2026

Published on: 15 October, 2025

Article ID: e18756921374917

Pages: 9

DOI: 10.2174/0118756921374917251002055229

Price: $65

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Abstract

Chemotherapy remains the cornerstone of cancer treatment, and has significantly improved patient survival. However, it is often accompanied by adverse effects that negatively impact quality of life, with neurotoxicity being one of the most debilitating yet often overlooked complications. This study aims to explore the influence of genetic variations on chemotherapy-induced neurotoxicity. Utilizing the PharmGKB database, we identified genetic variants associated with neurotoxic responses and assessed their Level of Evidence (LOE). Our findings highlight several genes, BCL2, OPRM1, SOX10, TRPV1, CYP3A4*22, GSK3β, DPYD, and ADORA2A, that are involved in neurotoxicity induced by chemotherapeutic agents, such as platinum/taxane, vincristine, fluorouracil, and methotrexate. These genetic factors modulate individual susceptibility to neurotoxic side effects. Understanding these associations supports the development of genotypeguided therapeutic strategies to reduce toxicity and improve quality of life in cancer patients receiving chemotherapy.

Keywords: Neurotoxicity, chemotherapy drugs, pharmacogenomics, bioinformatics, level of evidence, chemotherapeutic agents.

[1]
Stankovic, J.S.K.; Selakovic, D.; Mihailovic, V.; Rosic, G. Antioxidant supplementation in the treatment of neurotoxicity induced by platinum-based chemotherapeutics: A review. Int. J. Mol. Sci., 2020, 21(20), 7753.
[http://dx.doi.org/10.3390/ijms21207753] [PMID: 33092125]
[2]
Friedman, J.R.; Richbart, S.D.; Merritt, J.C. Capsaicinoids enhance chemosensitivity to chemotherapeutic drugs. Adv. Cancer Res., 2019, 144, 263-298.
[http://dx.doi.org/10.1016/bs.acr.2019.05.002] [PMID: 31349900]
[3]
Zhang, C.; Xu, C.; Gao, X.; Yao, Q. Platinum-based drugs for cancer therapy and anti-tumor strategies. Theranostics, 2022, 12(5), 2115-2132.
[http://dx.doi.org/10.7150/thno.69424] [PMID: 35265202]
[4]
Gatti, D.M.; Weber, S.N.; Goodwin, N.C.; Lammert, F.; Churchill, G.A. Genetic background influences susceptibility to chemotherapy-induced hematotoxicity. Pharmacogenomics J., 2018, 18(2), 319-330.
[http://dx.doi.org/10.1038/tpj.2017.23] [PMID: 28607509]
[5]
Marmiroli, P.; Riva, B.; Pozzi, E. Susceptibility of different mouse strains to oxaliplatin peripheral neurotoxicity: Phenotypic and genotypic insights. PLoS One, 2017, 12(10), e0186250.
[http://dx.doi.org/10.1371/journal.pone.0186250] [PMID: 29020118]
[6]
Tong, S.; Wang, Y.; Wu, J.; Long, J.; Zhong, P.; Wang, B. Comprehensive pharmacogenomics characterization of temozolomide response in gliomas. Eur. J. Pharmacol., 2021, 912, 174580.
[http://dx.doi.org/10.1016/j.ejphar.2021.174580] [PMID: 34678239]
[7]
Narendra, G.; Choudhary, S.; Raju, B.; Verma, H.; Silakari, O. Role of genetic polymorphisms in drug-metabolizing enzyme-mediated toxicity and pharmacokinetic resistance to anti-cancer agents: A review on the pharmacogenomics aspect. Clin. Pharmacokinet., 2022, 61(11), 1495-1517.
[http://dx.doi.org/10.1007/s40262-022-01174-7] [PMID: 36180817]
[8]
Ghanbarian, M.; Afgar, A.; Yadegarazari, R.; Najafi, R.; Teimoori-Toolabi, L. Through oxaliplatin resistance induction in colorectal cancer cells, increasing ABCB1 level accompanies decreasing level of miR-302c-5p, miR-3664-5p and miR-129-5p. Biomed. Pharmacother., 2018, 108, 1070-1080.
[http://dx.doi.org/10.1016/j.biopha.2018.09.112] [PMID: 30372807]
[9]
Pagnotta, P.; Melito, V.; Lavandera, J. Role of ABCB1 and glutathione S transferase gene variants in the association of porphyria cutanea tarda and human immunodeficiency virus infection. Biomed. Rep., 2020, 14(2), 22.
[http://dx.doi.org/10.3892/br.2020.1398] [PMID: 33335728]
[10]
Gumelar, G.; Ulfa, M.; Amukti, D. Harnessing genomic and bioinformatic data to broaden understanding of leukaemia across continents. Scr. Med. (Brno), 2024, 55(6), 717-725.
[http://dx.doi.org/10.5937/scriptamed55-51720]
[11]
Muhammad Irham, L.; Chou, W.H.; Wang, Y.S. Evaluation for the genetic association between store-operated calcium influx pathway (Stim1 and orai1) and human hepatocellular carcinoma in patients with chronic Hepatitis B infection. Biology, 2020, 9(11), 388.
[http://dx.doi.org/10.3390/biology9110388] [PMID: 33182378]
[12]
Irham, L.M.; Adikusuma, W.; Lolita, L. Investigation of susceptibility genes for chickenpox disease across multiple continents. Biochem. Biophys. Rep., 2023, 33, 101419.
[http://dx.doi.org/10.1016/j.bbrep.2022.101419] [PMID: 36620086]
[13]
Irham, L.M.; Amukti, D.P.; Adikusuma, W.; Singh, D.; Chong, R.; Basyuni, M. Applied of bioinformatics in drug discovery and drug development: Bioinformatic analysis 1996-2024. BIO Web Conf, 2024, 148, 01003.
[http://dx.doi.org/10.1051/bioconf/202414801003]
[14]
Humolungo, DTWS; Anjani, R; Irham, LM; Sulistyani, N; Ma’ruf, M; Amukti, DP Identification of pathogenic gene variants in carpal tunnel syndrome using bioinformatics approaches E3S Web of Conf, 2024, 501, 01022.
[http://dx.doi.org/10.1051/e3sconf/202450101022]
[15]
Yin, C.; Cao, Y.; Sun, P. Molecular subtyping of cancer based on robust graph neural network and multi-omics data integration. Front. Genet., 2022, 13, 884028.
[http://dx.doi.org/10.3389/fgene.2022.884028] [PMID: 35646077]
[16]
Sharifi-Noghabi, H.; Zolotareva, O.; Collins, C.C.; Ester, M. MOLI: Multi-omics late integration with deep neural networks for drug response prediction. Bioinformatics, 2019, 35(14), i501-i509.
[http://dx.doi.org/10.1093/bioinformatics/btz318] [PMID: 31510700]
[17]
Amukti, DP; Wazni, AR; Irham, LM Identifying pathogenic variants associated with Alzheimer by integrating genomic databases and bioinformatics approaches E3S Web Conf, 2024, 501, 01021.
[18]
Wing, C.; Komatsu, M.; Delaney, S.M.; Krause, M.; Wheeler, H.E.; Dolan, M.E. Application of stem cell derived neuronal cells to evaluate neurotoxic chemotherapy. Stem Cell Res. (Amst.), 2017, 22, 79-88.
[http://dx.doi.org/10.1016/j.scr.2017.06.006] [PMID: 28645005]
[19]
Ho, G.Y.; Woodward, N.; Coward, J.I.G. Cisplatin versus carboplatin: Comparative review of therapeutic management in solid malignancies. Crit. Rev. Oncol. Hematol., 2016, 102, 37-46.
[http://dx.doi.org/10.1016/j.critrevonc.2016.03.014] [PMID: 27105947]
[20]
McWhinney-Glass, S.; Winham, S.J.; Hertz, D.L. Cumulative genetic risk predicts platinum/taxane-induced neurotoxicity. Clin. Cancer Res., 2013, 19(20), 5769-5776.
[http://dx.doi.org/10.1158/1078-0432.CCR-13-0774] [PMID: 23963862]
[21]
de Graan, A.J.M.; Elens, L.; Sprowl, J.A. CYP3A4*22 genotype and systemic exposure affect paclitaxel-induced neurotoxicity. Clin. Cancer Res., 2013, 19(12), 3316-3324.
[http://dx.doi.org/10.1158/1078-0432.CCR-12-3786] [PMID: 23640974]
[22]
Park, S.B.; Kwok, J.B.; Loy, C.T. Paclitaxel-induced neuropathy: Potential association of MAPT and GSK3B genotypes. BMC Cancer, 2014, 14(1), 993.
[http://dx.doi.org/10.1186/1471-2407-14-993] [PMID: 25535399]
[23]
Gao, N.; Li, M.; Wang, W.; Liu, Z.; Guo, Y. The dual role of TRPV1 in peripheral neuropathic pain: Pain switches caused by its sensitization or desensitization. Front. Mol. Neurosci., 2024, 17, 1400118.
[http://dx.doi.org/10.3389/fnmol.2024.1400118] [PMID: 39315294]
[24]
Lucafò, M.; Stankovic, B.; Kotur, N. Pharmacotranscriptomic biomarkers in glucocorticoid treatment of pediatric inflammatory bowel disease. Curr. Med. Chem., 2018, 25(24), 2855-2871.
[http://dx.doi.org/10.2174/0929867324666170920145337] [PMID: 28933291]
[25]
Gutierrez-Camino, Á.; Umerez, M.; Martin-Guerrero, I. Mir-pharmacogenetics of Vincristine and peripheral neurotoxicity in childhood B-cell acute lymphoblastic leukemia. Pharmacogenomics J., 2018, 18(6), 704-712.
[http://dx.doi.org/10.1038/s41397-017-0003-3] [PMID: 29282364]
[26]
Sheikhnia, F.; Maghsoudi, H.; Majidinia, M. The critical function of microRNAs in developing resistance against 5- fluorouracil in cancer cells. Mini Rev. Med. Chem., 2024, 24(6), 601-617.
[http://dx.doi.org/10.2174/1389557523666230825144150] [PMID: 37642002]
[27]
Diasio, R.B.; Beavers, T.L.; Carpenter, J.T. Familial deficiency of dihydropyrimidine dehydrogenase. Biochemical basis for familial pyrimidinemia and severe 5-fluorouracil-induced toxicity. J. Clin. Invest., 1988, 81(1), 47-51.
[http://dx.doi.org/10.1172/JCI113308] [PMID: 3335642]
[28]
Schroyen, G.; Meylaers, M.; Deprez, S. Prevalence of leukoencephalopathy and its potential cognitive sequelae in cancer patients. J. Chemother., 2020, 32(7), 327-343.
[http://dx.doi.org/10.1080/1120009X.2020.1805239] [PMID: 32799637]
[29]
AlKawi, A.; Hanbali, A.; Haj Aissa, N.; Mufti, M.A.; Abdul Rab, S. Recurrence of methotrexate-induced leukoencephalopathy after methotrexate rechallenge: A case report and literature review. Radiol. Case Rep., 2023, 18(3), 799-804.
[http://dx.doi.org/10.1016/j.radcr.2022.11.057] [PMID: 36582751]
[30]
Debom, G.N.; Rubenich, D.S.; Braganhol, E. Adenosinergic signaling as a key modulator of the glioma microenvironment and reactive astrocytes. Front. Neurosci., 2022, 15, 648476.
[http://dx.doi.org/10.3389/fnins.2021.648476] [PMID: 35069091]
[31]
Tsujimoto, S.; Yanagimachi, M.; Tanoshima, R. Influence of ADORA2A gene polymorphism on leukoencephalopathy risk in MTX‐treated pediatric patients affected by hematological malignancies. Pediatr. Blood Cancer, 2016, 63(11), 1983-1989.
[http://dx.doi.org/10.1002/pbc.26090] [PMID: 27399166]
[32]
Amukti, D.P.; Irham, L.M.; Pratami, R.I.; Adikusuma, W. Identifying Gene variants that are pathogenic in osteoporosis using an omics data and bioinformatics approach. Biom J Ind, 2024, 10(3), 104-111.
[http://dx.doi.org/10.32539/bji.v10i3.199]
[33]
Irham, L.M.; Amukti, D.P.; Adikusuma, W.; Singh, D.; Chong, R.; Pranata, S. Trends in drug repurposing for chronic hepatitis-B infection:bibliometric-basedapproach1990-2024. BIO Web of Conf, 2025, 148
[http://dx.doi.org/10.1051/bioconf/202414804003]
[34]
Made, I.; Wijaya, H.; Fahrian Hipmi, A.; Nur, S.; Abas, R.; Amukti, D.P. Potential of fgl1 gene variation in increasing liver side effect risk due to nifedipine use in gestational hypertension patients. JIFFK, 2024, 21(2), 269.
[35]
Amukti, D.P.; Irham, L.M.; Surono, S.; El Khair, R.; Adikusuma, W.; Satria, R. Atherosclerosis research in the genomic era: Global trends from 1983 to 2024. Bulgar Cardiol, 2024, 30(4), 40-48.
[http://dx.doi.org/10.3897/bjcardio.30.e143367]
[36]
Akhilesh, U.A.; Uniyal, A.; Gadepalli, A. Unlocking the potential of TRPV1 based siRNA therapeutics for the treatment of chemotherapy-induced neuropathic pain. Life Sci., 2022, 288, 120187.
[http://dx.doi.org/10.1016/j.lfs.2021.120187] [PMID: 34856209]
[37]
Egan-Sherry, D.; Bhuta, R.; Cole, P.D. Severe vincristine-related neurotoxicity in 5 patients with pediatric acute lymphoblastic leukemia requiring discontinuation of vincristine: A description of long-term outcome. J. Pediatr. Hematol. Oncol., 2021, 43(7), e997-e999.
[http://dx.doi.org/10.1097/MPH.0000000000002114] [PMID: 34001785]
[38]
Ahmed, H.S.; Thrishulamurthy, C.J. Vincristine-induced ptosis in pediatric patients: A systematic review and practice recommendations. Eur. J. Pediatr., 2025, 184(3), 209.
[http://dx.doi.org/10.1007/s00431-025-06039-2] [PMID: 39994116]

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