ArticleThe pharmacogenomics journal2011
Polymorphisms in cytochromes P450 2C8 and 3A5 are associated with paclitaxel neurotoxicity.
Article in The pharmacogenomics journal, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 3 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
54 citing papers in PubMed, 3 syntheses or guidelines pooled it, 127 citations in OpenAlex.
- Why pharmacogenomic biomarkers for chemotherapy-induced peripheral neuropathy fail: a systematic review of genetic associations, replication, and clinical translation.Frontiers in pharmacology · 2026Pooled it
- Pharmacogenetics of taxane-induced neurotoxicity in breast cancer: Systematic review and meta-analysis.Clinical and translational science · 2022Pooled it
- Testing of candidate single nucleotide variants associated with paclitaxel neuropathy in the trial NCCTG N08C1 (Alliance).Cancer medicine · 2016Pooled it
- Genotypes of CYP2C8 and FGD4 and their association with peripheral neuropathy or early dose reduction in paclitaxel-treated breast cancer patients.British journal of cancer · 2016Trial
- Polygenic inheritance of paclitaxel-induced sensory peripheral neuropathy driven by axon outgrowth gene sets in CALGB 40101 (Alliance).The pharmacogenomics journal · 2014Trial
- Randomised phase II study comparing dose-escalated weekly paclitaxel vs standard-dose weekly paclitaxel for patients with previously treated advanced gastric cancer.British journal of cancer · 2014Trial
- A genome-wide association study identifies novel loci for paclitaxel-induced sensory peripheral neuropathy in CALGB 40101.Clinical cancer research : an official journal of the American Association for Cancer Research · 2012Trial
- Impact of SLCO1B3 767G>C (rs60140950) polymorphism on paclitaxel response in Iraqi women with breast cancer.Journal of Taibah University Medical Sciences · 2026Article
- Proximity Labelling Reveals the Compartmental Proteome of Murine Sensory Neurons.European journal of pain (London, England) · 2026Article
- Hydrogen-Bond-Assisted Catalysis: Hydroxylation of Paclitaxel by Human CYP2C8.Journal of the American Chemical Society · 2024Article
- Review
- Potential Association of Cytochrome P450 Copy Number Alteration in Tumour with Chemotherapy Resistance in Lung Adenocarcinoma Patients.International journal of molecular sciences · 2023Article
- Cytochrome P450 Oxidoreductase (POR) Associated with Severe Paclitaxel-Induced Peripheral Neuropathy in Patients of European Ancestry from ECOG-ACRIN E5103.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- The impact of single nucleotide polymorphisms on return-to-work after taxane-based chemotherapy in breast cancer.Cancer chemotherapy and pharmacology · 2023Article
- The Quantification of Paclitaxel and Its Two Major Metabolites in Biological Samples by HPLC-MS/MS and Its Application in a Pharmacokinetic and Tumor Distribution Study in Xenograft Nude Mouse.Molecules (Basel, Switzerland) · 2023Article
- Article
- Genetic variations that influence paclitaxel pharmacokinetics and intracellular effects that may contribute to chemotherapy-induced neuropathy: A narrative review.Frontiers in pain research (Lausanne, Switzerland) · 2023Review
- Construction of Curcumin and Paclitaxel Co-Loaded Lipid Nano Platform and Evaluation of Its Anti-Hepatoma Activity in vitro and Pharmacokinetics in vivo.International journal of nanomedicine · 2023Article
- Solute Carrier Transportome in Chemotherapy-Induced Adverse Drug Reactions.Reviews of physiology, biochemistry and pharmacology · 2022Article
- Management of Side Effects in the Personalized Medicine Era: Chemotherapy-Induced Peripheral Neurotoxicity.Methods in molecular biology (Clifton, N.J.) · 2022Article
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neurotoxicity is one of the most relevant dose-limiting toxicities of the anticancer drug paclitaxel. It exhibits substantial interindividual variability of unknown molecular basis, and represents one of the major challenges for the improvement of paclitaxel therapy. The extensive variability in paclitaxel clearance and metabolism lead us to investigate the association between polymorphisms in paclitaxel elimination pathway and neurotoxicity. We selected 13 relevant polymorphisms in genes encoding paclitaxel metabolizing enzymes (CYP2C8, CYP3A4 and CYP3A5) and transporters (organic anion transporting polypeptide (OATP) 1B1, OATP1B3 and P-glycoprotein) and genotyped them in 118 Spanish cancer patients treated with paclitaxel. After adjusting for age and treatment schedule, CYP2C8 Haplotype C and CYP3A5*3 were associated with protection (hazard ratio (HR) (per allele)=0.55; 95% confidence interval (CI)=0.34-0.89; P=0.014 and HR (per allele)=0.51; 95%CI=0.30-0.86; and P=0.012, respectively) and CYP2C8*3 with increased risk (HR (per allele)=1.72; 95%CI=1.05-2.82; and P=0.032). In each case, the allele causing increased paclitaxel metabolism was associated with increased neurotoxicity, suggesting an important role for metabolism and hydroxylated paclitaxel metabolites. We estimated the HR per paclitaxel-metabolism increasing allele carried across the three polymorphisms to be HR=1.64 (95% CI=1.26-2.14; P=0.0003). The results for P-glycoprotein were inconclusive, and no associations were observed for the other genes studied. The incorporation of this genetic data in treatment selection could help to reduce neurotoxicity events, thereby individualizing paclitaxel pharmacotherapy. These results warrant validation in independent series.
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