ArticleBritish journal of clinical pharmacology2020
Genetic variation in EPHA contributes to sensitivity to paclitaxel-induced peripheral neuropathy.
Article in British journal of clinical pharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it, 17 citations in OpenAlex.
- Pharmacogenetics of taxane-induced neurotoxicity in breast cancer: Systematic review and meta-analysis.Clinical and translational science · 2022Pooled it
- Quantitation of Plasma Proteins to Predict Taxane-Induced Peripheral Neuropathy.JCO precision oncology · 2025Article
- ECOG-ACRIN EAZ171: Prospective Validation Trial of Germline Predictors of Taxane-Induced Peripheral Neuropathy in Black Women With Early-Stage Breast Cancer.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2024Article
- Evolution of predictive risk factor analysis for chemotherapy-related toxicity.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2023Review
- A Systematic Review of Polygenic Models for Predicting Drug Outcomes.Journal of personalized medicine · 2022Review
- Mechanistic insights into the pathogenesis of microtubule-targeting agent-induced peripheral neuropathy from pharmacogenetic and functional studies.Basic & clinical pharmacology & toxicology · 2022Review
- Biomarkers of Chemotherapy-Induced Peripheral Neuropathy: Current Status and Future Directions.Frontiers in pain research (Lausanne, Switzerland) · 2022Review
- Management of Side Effects in the Personalized Medicine Era: Chemotherapy-Induced Peripheral Neurotoxicity.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Analysis Approaches to Identify Pharmacogenetic Associations With Pharmacodynamics.Clinical pharmacology and therapeutics · 2021Review
- Exploring pharmacogenetics of paclitaxel- and docetaxel-induced peripheral neuropathy by evaluating the direct pharmacogenetic-pharmacokinetic and pharmacokinetic-neuropathy relationships.Expert opinion on drug metabolism & toxicology · 2021Review
- Transcriptome Remodeling in Gradual Development of Inverse Resistance between Paclitaxel and Cisplatin in Ovarian Cancer Cells.International journal of molecular sciences · 2020Article
- Genetic variation in Charcot-Marie-Tooth genes contributes to sensitivity to paclitaxel-induced peripheral neuropathy.Pharmacogenomics · 2020Observational
- Genetic variation in EPHA contributes to sensitivity to paclitaxel-induced peripheral neuropathy.British journal of clinical pharmacology · 2020Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
Abstract
aimsChemotherapy-induced peripheral neuropathy (PN) is a treatment limiting toxicity of paclitaxel. We evaluated if EPHA genetic variation (EPHA4, EPHA5, EPHA6, and EPHA8) is associated with PN sensitivity by accounting for variability in systemic paclitaxel exposure (time above threshold).
methodsGermline DNA from 60 patients with breast cancer was sequenced. PN was measured using the 8-item sensory subscale (CIPN8) of the patient-reported CIPN20. Associations for 3 genetic models were tested by incorporating genetics into previously published PN prediction models integrating measured paclitaxel exposure and cumulative treatment. Significant associations were then tested for association with PN-related treatment disruption.
resultsEPHA5 rs7349683 (minor allele frequency = 0.32) was associated with increased PN sensitivity (β-coefficient = 0.39, 95% confidence interval 0.11-0.67, p = 0.007). Setting a maximum tolerable threshold of CIPN8 = 30, optimal paclitaxel exposure target is shorter for rs7349683 homozygous (11.6 h) than heterozygous (12.6 h) or wild-type (13.6 h) patients. Total number of missense variants (median = 0, range 0-2) was associated with decreased PN sensitivity (β-coefficient: -0.42, 95% confidence interval -0.72 to -0.12, P = .006). No association with treatment disruption was detected for the total number of missense variants or rs7349683.
conclusionIsolating toxicity sensitivity by accounting for exposure is a novel approach, and rs7349683 represents a promising marker for PN sensitivity that may be used to individualize paclitaxel treatment.
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