Predictors of cisplatin-induced ototoxicity and survival in chemoradiation treated head and neck cancer patients

Teft, Wendy A.; Winquist, Eric; Nichols, Anthony C.; Kuruvilla, Sara; Richter, Suzanne; Parker, Christina; Francis, Princy; Trinnear, M.; Lukovic, Jelena; Bukhari, Nedal; Choi, Yunhee; Welch, Stephen; Palma, David A.; Palma, David A.; Kim, Richard B.

doi:10.1016/j.oraloncology.2018.12.010

Cited by 35 publications

(32 citation statements)

References 33 publications

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“…Further support for this variant has been provided by three independent studies that have replicated the association with ACYP2 and CIO . Two studies were, however, unable to replicate these findings ( Table ), the results of which have not yet been recorded in the PharmGKB database.…”

Section: Validation Of Pharmacogenomic Association Resultsmentioning

confidence: 99%

“…The TPMT and COMT associations have been investigated in multiple cohorts, and although some studies have replicated these associations, others were unable to confirm these findings ( Table and Table ). These conflicting results may in part be attributed to the heterogeneity of the cohorts under investigation, as discussed in more detail in the section “Confounding Factors.” Of note, when excluding cohorts of patients who all received cranial irradiation or that included adult patients, the findings from all but one study showed that TPMT rs12201199 was either significantly more frequent in cases when compared with controls, or trended toward significance ( P = 0.07) . On closer examination of the small cohort of patients ( n = 41) that deviated from the pattern of increased risk, it was observed that only CIO cases carried nonfunctional TPMT*3 alleles.…”

Section: Validation Of Pharmacogenomic Association Resultsmentioning

confidence: 99%

“…In addition, von Stechow et al 29 demonstrated that TPMT expression is induced by cisplatin in embryonic stem cells, providing further evidence for this drug-gene relationship. The TPMT and COMT associations have been investigated in multiple cohorts, and although some studies have replicated these associations, 23,[30][31][32][33] others were unable to confirm these findings 9,13,16,30,[32][33][34][35][36] (Table 1 and Table S1). These conflicting results may in part be attributed to the heterogeneity of the cohorts under investigation, as discussed in more detail in the section "Confounding Factors."…”

Section: Supporting Evidence For the Roles Of Comt And Tpmt In Ciomentioning

confidence: 99%

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Pharmacogenomics of Cisplatin‐Induced Ototoxicity: Successes, Shortcomings, and Future Avenues of Research

Drögemöller

Wright

et al. 2019

Clin Pharma and Therapeutics

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Cisplatin is a highly effective chemotherapeutic. Unfortunately, its use is limited by cisplatin‐induced ototoxicity (CIO). Substantial research has been performed to uncover the genetic variants associated with CIO; however, there has been a lack of consistency in the results that have been reported. This paper aims to provide an overview of the current state of CIO genomics research, delving into the shortcomings of past research, and providing recommendations for future avenues of study.

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Section: Validation Of Pharmacogenomic Association Resultsmentioning

confidence: 99%

Section: Validation Of Pharmacogenomic Association Resultsmentioning

confidence: 99%

Section: Supporting Evidence For the Roles Of Comt And Tpmt In Ciomentioning

confidence: 99%

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Pharmacogenomics of Cisplatin‐Induced Ototoxicity: Successes, Shortcomings, and Future Avenues of Research

Drögemöller

Wright

et al. 2019

Clin Pharma and Therapeutics

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“…However, none of the OCT genetic variants was proven to be associated with cisplatin-induced ototoxicity. Through candidate gene studies, rs9332377 COMT [106][107][108] and rs12201199 TPMT [106,109,110] were associated with ototoxicity, although the direction of association is not consistent among studies. Meanwhile, the rs4788863 SLC16A5 variant demonstrated an otoprotective effect [111,112].…”

Section: Impact Of Pharmacogenetic Variants In Octs In Precision Medimentioning

confidence: 96%

The Impact of Genetic Polymorphisms in Organic Cation Transporters on Renal Drug Disposition

Zazuli

Duin

Jansen

et al. 2020

IJMS

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A considerable number of drugs and/or their metabolites are excreted by the kidneys through glomerular filtration and active renal tubule secretion via transporter proteins. Uptake transporters in the proximal tubule are part of the solute carrier (SLC) superfamily, and include the organic cation transporters (OCTs). Several studies have shown that specific genetic polymorphisms in OCTs alter drug disposition and may lead to nephrotoxicity. Multiple single nucleotide polymorphisms (SNPs) have been reported for the OCT genes (SLC22A1, SLC22A2 and SLC22A3), which can influence the proteins’ structure and expression levels and affect their transport function. A gain-in-function mutation may lead to accumulation of drugs in renal proximal tubule cells, eventually leading to nephrotoxicity. This review illustrates the impact of genetic polymorphisms in OCTs on renal drug disposition and kidney injury, the clinical significances and how to personalize therapies to minimize the risk of drug toxicity.

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“…In ovarian cancer, upregulation of miR‐490‐3p enhanced the sensitivity of ovarian cancer cells to DDP by downregulating ABCC2 expression 11 . In addition, upregulation of ABCC2 and ABCG2 transporters was observed in head and neck squamous cell carcinoma cell lines with cytoplasmically sequestered mutant p53, and these cell lines were frequently found to be more resistant to DDP 12,13 . ABCC2 inhibition of head and neck squamous cell carcinoma cells with MK571 markedly enhanced the sensitivity of HNSCC cells to DDP 14‐16 .…”

Section: Introductionmentioning

confidence: 99%

Increased ABCC2 expression predicts cisplatin resistance in non‐small cell lung cancer

Chen

Zhou

Yang

et al. 2020

Cell Biochemistry & Function

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Long‐term use of platinum‐based drugs can cause non‐small cell lung cancer (NSCLC) to develop extremely strong drug resistance. Increasing the drug dosage does not have better treatment effects and could lead to serious complications. High levels of drug resistance are considered to be characteristic of human tumours and are usually mediated by genes related to multidrug resistance. Multidrug resistance‐associated protein 2 (ABCC2), an ATP‐binding cassette multidrug resistance transporter, was found to be overexpressed in various human cancers. In this study, we found that ABCC2 was also upregulated in cisplatin (DDP)‐resistant A549 cells (A549/DDP). Functional studies demonstrated that ABCC2 knockdown reversed DDP resistance and promoted G1 phase arrest in A549/DDP cells, and PARP and caspase‐3 were activated in A549/DDP cells following ABCC2 knockdown. In vivo, ABCC2 knockdown enhanced the cytotoxicity of DDP to subcutaneous A549 tumours. Together, these results suggest that ABCC2 may be a potential therapeutic strategy for overcoming DDP resistance in NSCLC patients. Significance of the study In this study, we investigated the role of ABCC2 in cisplatin resistance of NSCLC cells. Our data show that ABCC2 expression was associated with resistance to cisplatin and that knockdown ABCC2 could reverse cisplatin resistance in NSCLC cells. Taken together, our study suggests that reducing the expression of ABCC2 could become an important strategy for enhancing the sensitivity of NSCLC cells to cisplatin.

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Predictors of cisplatin-induced ototoxicity and survival in chemoradiation treated head and neck cancer patients

Cited by 35 publications

References 33 publications

Pharmacogenomics of Cisplatin‐Induced Ototoxicity: Successes, Shortcomings, and Future Avenues of Research

Pharmacogenomics of Cisplatin‐Induced Ototoxicity: Successes, Shortcomings, and Future Avenues of Research

The Impact of Genetic Polymorphisms in Organic Cation Transporters on Renal Drug Disposition

Increased ABCC2 expression predicts cisplatin resistance in non‐small cell lung cancer

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