Liability of the Voltage-Gated Sodium Channel Gene &lt;i&gt;SCN2A&lt;/i&gt; R19K Polymorphism to Oxaliplatin-Induced Peripheral Neuropathy

Argyriou, Andreas A.; Antonacopoulou, Anna G.; Scopa, Chrisoula D.; Κοττόρου, Αναστασία; Kominea, Athina; Peroukides, Stavros; Kalofonos, Haralabos P.

doi:10.1159/000236049

Cited by 19 publications

(9 citation statements)

References 16 publications

(8 reference statements)

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“…Despite similar co-morbidities, demographic profile, cancer stage and treatment schedule, oxaliplatin-treated patients can develop OIPN with different severity [ 10 ]. Individual variability in drug toxicity response has suggested that specific genetic variants determining over-expression or down-regulation of genes involved in drug disposition, metabolism, detoxification, channels functioning and DNA repair could be associated with OIPN susceptibility and severity [ 11 – 16 ], but this still remains a matter of scientific debate [ 5 , 17 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

Susceptibility of different mouse strains to oxaliplatin peripheral neurotoxicity: Phenotypic and genotypic insights

et al. 2017

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Peripheral neurotoxicity is one of the most distressing side effects of oxaliplatin therapy for cancer. Indeed, most patients that received oxaliplatin experience acute and/or chronic severe sensory peripheral neuropathy. However, despite similar co-morbidities, cancer stage, demographics and treatment schedule, patients develop oxaliplatin-induced peripheral neurotoxicity with remarkably different severity. This suggests individual genetic variability, which might be used to glean the mechanistic insights into oxaliplatin neurotoxicity. We characterized the susceptibility of different mice strains to oxaliplatin neurotoxicity investigating the phenotypic features of neuropathy and gene expression profiles in dorsal root ganglia of six genetically different mice strains (Balb-c, C57BL6, DBA/2J, AJ, FVB and CD1) exposed to the same oxaliplatin schedule. Differential gene expression in dorsal root ganglia from each mice strain were assayed using a genome-wide expression analysis and selected genes were validated by RT-PCR analysis. The demonstration of consistent differences in the phenotypic response to oxaliplatin across different strains is interesting to allow the selection of the appropriate strain based on the pre-defined read-out parameters. Further investigation of the correlation between gene expression changes and oxaliplatin-induced neurotoxicity phenotype in each strain will be useful to deeper investigate the molecular mechanisms of oxaliplatin neurotoxicity.

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Section: Introductionmentioning

confidence: 99%

Susceptibility of different mouse strains to oxaliplatin peripheral neurotoxicity: Phenotypic and genotypic insights

et al. 2017

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“…The SCN2A R19K polymorphism failed to be associated with liability to OXAIPN in a study in which 62 advanced CRC patients were genotyped [ 113 ]. Similarly, no significant association emerged between SCN9A variant rs6746030 and OXAIPN in a subsequent study comprising 200 CRC patients [ 114 ], contrasting the results of a smaller study in which SCN9A rs6746030 was protective of severe OXAIPN in a heterogeneous population of 94 patients with various digestive tract cancers, and an increased incidence of coexisting diabetes (24%) in patients with grade 3–4 OXAIPN [ 115 ].…”

Section: Pharmacogenomic Biomarkersmentioning

confidence: 99%

Predictive Biomarkers of Oxaliplatin-Induced Peripheral Neurotoxicity

Velasco

Alemany

Villagrán

et al. 2021

JPM

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Oxaliplatin (OXA) is a platinum compound primarily used in the treatment of gastrointestinal cancer. OXA-induced peripheral neurotoxicity (OXAIPN) is the major non-hematological dose-limiting toxicity of OXA-based chemotherapy and includes acute transient neurotoxic effects that appear soon after OXA infusion, and chronic non-length dependent sensory neuronopathy symmetrically affecting both upper and lower limbs in a stocking-and-glove distribution. No effective strategy has been established to reverse or treat OXAIPN. Thus, it is necessary to early predict the occurrence of OXAIPN during treatment and possibly modify the OXA-based regimen in patients at high risk as an early diagnosis and intervention may slow down neuropathy progression. However, identifying which patients are more likely to develop OXAIPN is clinically challenging. Several objective and measurable early biomarkers for OXAIPN prediction have been described in recent years, becoming useful for informing clinical decisions about treatment. The purpose of this review is to critically review data on currently available or promising predictors of OXAIPN. Neurological monitoring, according to predictive factors for increased risk of OXAIPN, would allow clinicians to personalize treatment, by monitoring at-risk patients more closely and guide clinicians towards better counseling of patients about neurotoxicity effects of OXA.

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“…The literature contains reports suggesting increased susceptibility to OXAIPN with pharmacogenetic variations in genes encoding for drug transporters ( ABCC1 and ABCG1 genes), detoxification enzymes ( MPO , GSTA1 , GSTM1/3 , GSTP1 and GSTT1), DNA repair mechanisms ( ERCC2 , XPA , XRCC1 and ERCC1 ) and integrin B3 (an integral cell-surface protein known to participate in cell adhesion and in cell surface-mediated signaling) Leu33Pro polymorphism [ 9 , 34 , 35 , 36 ]. Further SCNA SNPs, such as the SCN2A R19K polymorphism, have been tested and found not related to OXAIPN manifestation [ 37 ].…”

Section: Pharmacogeneticsmentioning

confidence: 99%

Updates on Oxaliplatin-Induced Peripheral Neurotoxicity (OXAIPN)

Argyriou

2015

Toxics

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Oxaliplatin-induced peripheral neuropathy (OXAIPN) is of great clinical interest as it ranks among the most common dose limiting toxicities of oxaliplatin (OXA) administration with an obvious impact on the outcome of cancer patients. In addition, OXAIPN has a detrimental effect on the quality of life of cancer patients because it can be long lasting or even permanent. It has a unique spectrum of clinical presentation, being manifested with two distinct syndromes: the acute neurotoxicity that appears soon after OXA administration and is usually transient, and the chronic cumulative syndrome that resembles the characteristics of all platinum compounds. Despite advances in research in relation to the elucidation of the true OXAIPN pathogenesis, characteristics and management, there are still several open issues to be addressed. One of the most important open issues is to determine reliable biomarkers to allow prompt identification of patients at high risk to develop OXAIPN and towards this view well designed genome wide analyses are warranted to adequately address this gap in knowledge. Recent updates are provided in this article in relation to the pathogenesis, clinical characteristics, pharmacogenetics and management of OXAIPN.

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Liability of the Voltage-Gated Sodium Channel Gene <i>SCN2A</i> R19K Polymorphism to Oxaliplatin-Induced Peripheral Neuropathy

Cited by 19 publications

References 16 publications

Susceptibility of different mouse strains to oxaliplatin peripheral neurotoxicity: Phenotypic and genotypic insights

Susceptibility of different mouse strains to oxaliplatin peripheral neurotoxicity: Phenotypic and genotypic insights

Predictive Biomarkers of Oxaliplatin-Induced Peripheral Neurotoxicity

Updates on Oxaliplatin-Induced Peripheral Neurotoxicity (OXAIPN)

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