ArticleClinical cancer research : an official journal of the American Association for Cancer Research2015
Pharmacoethnicity in Paclitaxel-Induced Sensory Peripheral Neuropathy.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 3 of them syntheses that pooled it.
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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.
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Who cites it
28 citing papers in PubMed, 3 syntheses or guidelines pooled it, 53 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
- Genomewide Meta-Analysis Validates a Role for S1PR1 in Microtubule Targeting Agent-Induced Sensory Peripheral Neuropathy.Clinical pharmacology and therapeutics · 2020Pooled it
- Weekly dose-dense chemotherapy in first-line epithelial ovarian, fallopian tube, or primary peritoneal carcinoma treatment (ICON8): primary progression free survival analysis results from a GCIG phase 3 randomised controlled trial.Lancet (London, England) · 2019Trial
- Pharmacogenetic Discovery in CALGB (Alliance) 90401 and Mechanistic Validation of a VAC14 Polymorphism that Increases Risk of Docetaxel-Induced Neuropathy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2016Trial
- Emerging targets and translational challenges in treating paclitaxel-induced peripheral neuropathy.Molecular biology reports · 2025Review
- Prediction of response to promising first-line chemotherapy in ovarian cancer patients with residual peritoneal tumors: practical biomarkers and robust multiplex models.International journal of clinical oncology · 2024Article
- Optimization of a human induced pluripotent stem cell-derived sensory neuron model for the in vitro evaluation of taxane-induced neurotoxicity.Scientific reports · 2024Article
- Prediction models of persistent taxane-induced peripheral neuropathy among breast cancer survivors using whole-exome sequencing.NPJ precision oncology · 2024Article
- Paclitaxel therapeutic drug monitoring - International association of therapeutic drug monitoring and clinical toxicology recommendations.European journal of cancer (Oxford, England : 1990) · 2024Review
- Pharmacogenomic and Statistical Analysis.Methods in molecular biology (Clifton, N.J.) · 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
- Management of Side Effects in the Personalized Medicine Era: Chemotherapy-Induced Peripheral Neurotoxicity.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Mechanistic insights into the pathogenesis of microtubule-targeting agent-induced peripheral neuropathy from pharmacogenetic and functional studies.Basic & clinical pharmacology & toxicology · 2022Review
- Considerations for a Reliable In Vitro Model of Chemotherapy-Induced Peripheral Neuropathy.Toxics · 2021Review
- Developing nociceptor-selective treatments for acute and chronic pain.Science translational medicine · 2021Article
- Genetically regulated expression underlies cellular sensitivity to chemotherapy in diverse populations.Human molecular genetics · 2021Article
- Human Induced Pluripotent Stem Cell Derived Sensory Neurons are Sensitive to the Neurotoxic Effects of Paclitaxel.Clinical and translational science · 2021Article
- First-Line Management of Advanced High-Grade Serous Ovarian Cancer.Current oncology reports · 2020Review
Corrections and comments
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
Abstract
purposePaclitaxel is used worldwide in the treatment of breast, lung, ovarian, and other cancers. Sensory peripheral neuropathy is an associated adverse effect that cannot be predicted, prevented, or mitigated. To better understand the contribution of germline genetic variation to paclitaxel-induced peripheral neuropathy, we undertook an integrative approach that combines genome-wide association study (GWAS) data generated from HapMap lymphoblastoid cell lines (LCL) and Asian patients.
methodsGWAS was performed with paclitaxel-induced cytotoxicity generated in 363 LCLs and with paclitaxel-induced neuropathy from 145 Asian patients. A gene-based approach was used to identify overlapping genes and compare with a European clinical cohort of paclitaxel-induced neuropathy. Neurons derived from human-induced pluripotent stem cells were used for functional validation of candidate genes.
resultsSNPs near AIPL1 were significantly associated with paclitaxel-induced cytotoxicity in Asian LCLs (P < 10(-6)). Decreased expression of AIPL1 resulted in decreased sensitivity of neurons to paclitaxel by inducing neurite morphologic changes as measured by increased relative total outgrowth, number of processes and mean process length. Using a gene-based analysis, there were 32 genes that overlapped between Asian LCL cytotoxicity and Asian patient neuropathy (P < 0.05), including BCR. Upon BCR knockdown, there was an increase in neuronal sensitivity to paclitaxel as measured by neurite morphologic characteristics.
conclusionsWe identified genetic variants associated with Asian paclitaxel-induced cytotoxicity and functionally validated the AIPL1 and BCR in a neuronal cell model. Furthermore, the integrative pharmacogenomics approach of LCL/patient GWAS may help prioritize target genes associated with chemotherapeutic-induced peripheral neuropathy.
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Registered trials
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.