ArticleClinical cancer research : an official journal of the American Association for Cancer Research2013
Integration of cell line and clinical trial genome-wide analyses supports a polygenic architecture of Paclitaxel-induced sensory peripheral neuropathy.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.
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Who cites it
40 citing papers in PubMed, 1 synthesis or guideline pooled it, 59 citations in OpenAlex.
- Pharmacogenetics of taxane-induced neurotoxicity in breast cancer: Systematic review and meta-analysis.Clinical and translational science · 2022Pooled it
- Influence of LGALS3 polymorphisms on chemotherapy-induced peripheral neuropathy in patients with metastatic pancreatic cancer treated with gemcitabine and nab-paclitaxel: an exploratory biomarker analysis of the GENESECT study.Investigational new drugs · 2026Article
- Review of the contribution of clinical and genetic factors to the racial disparity in taxane-induced peripheral neuropathy.Critical reviews in oncology/hematology · 2025Review
- siRNA Treatments for Diabetic Neuropathy: Obstacles and Delivery Techniques.Current molecular medicine · 2025Review
- RFX2 promotes tumor cell stemness through epigenetic regulation of PAF1 in spinal ependymoma.Journal of neuro-oncology · 2023Article
- Polygenic risk of paclitaxel-induced peripheral neuropathy: a genome-wide association study.Journal of translational medicine · 2022Article
- Co-occurrence and metabolic biomarkers of sensory and motor subtypes of peripheral neuropathy from paclitaxel.Breast cancer research and treatment · 2022Article
- Mechanistic insights into the pathogenesis of microtubule-targeting agent-induced peripheral neuropathy from pharmacogenetic and functional studies.Basic & clinical pharmacology & toxicology · 2022Review
- A Grant-Based Experiment to Train Clinical Investigators: The AACR/ASCO Methods in Clinical Cancer Research Workshop.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Article
- Human Induced Pluripotent Stem Cell Derived Sensory Neurons are Sensitive to the Neurotoxic Effects of Paclitaxel.Clinical and translational science · 2021Article
- Pathogenesis of paclitaxel-induced peripheral neuropathy: A current review of in vitro and in vivo findings using rodent and human model systems.Experimental neurology · 2020Review
- Integration of genetic and functional genomics data to uncover chemotherapeutic induced cytotoxicity.The pharmacogenomics journal · 2019Article
- Synergistic Chemotherapy Drug Response Is a Genetic Trait in Lymphoblastoid Cell Lines.Frontiers in genetics · 2019Article
- Gene Network Dysregulation in the Trigeminal Ganglia and Nucleus Accumbens of a Model of Chronic Migraine-Associated Hyperalgesia.Frontiers in systems neuroscience · 2018Article
- Chemotherapy-induced peripheral neurotoxicity: management informed by pharmacogenetics.Nature reviews. Neurology · 2017Review
- Discovery of Novel Human Gene Regulatory Modules from Gene Co-expression and Promoter Motif Analysis.Scientific reports · 2017Article
- Application of stem cell derived neuronal cells to evaluate neurotoxic chemotherapy.Stem cell research · 2017Article
- Chemotherapy-induced peripheral neuropathy: A current review.Annals of neurology · 2017Review
- Genetic Variants Contributing to Colistin Cytotoxicity: Identification of TGIF1 and HOXD10 Using a Population Genomics Approach.International journal of molecular sciences · 2017Article
- Integrative genetic analysis suggests that skin color modifies the genetic architecture of melanoma.PloS one · 2017Article
Corrections and comments
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Authors and funding
21 authors at 6 institutions in 2 countries.
Funding
Abstract
purposeWe sought to show the relevance of a lymphoblastoid cell line (LCL) model in the discovery of clinically relevant genetic variants affecting chemotherapeutic response by comparing LCL genome-wide association study (GWAS) results to clinical GWAS results. EXPERIMENTAL
designA GWAS of paclitaxel-induced cytotoxicity was conducted in 247 LCLs from the HapMap Project and compared with a GWAS of sensory peripheral neuropathy in patients with breast cancer (n = 855) treated with paclitaxel in the Cancer and Leukemia Group B (CALGB) 40101 trial. Significant enrichment was assessed by permutation resampling analysis.
resultsWe observed an enrichment of LCL cytotoxicity-associated single-nucleotide polymorphisms (SNP) in the sensory peripheral neuropathy-associated SNPs from the clinical trial with concordant allelic directions of effect (empirical P = 0.007). Of the 24 SNPs that overlap between the clinical trial (P < 0.05) and the preclinical cytotoxicity study (P < 0.001), 19 of them are expression quantitative trait loci (eQTL), which is a significant enrichment of this functional class (empirical P = 0.0447). One of these eQTLs is located in RFX2, which encodes a member of the DNA-binding regulatory factor X family. Decreased expression of this gene by siRNA resulted in increased sensitivity of Neuroscreen-1(NS-1; rat pheochromocytoma) cells to paclitaxel as measured by reduced neurite outgrowth and increased cytotoxicity, functionally validating the involvement of RFX2 in nerve cell response to paclitaxel.
conclusionsThe enrichment results and functional example imply that cellular models of chemotherapeutic toxicity may capture components of the underlying polygenic architecture of related traits in patients.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.