ArticleGenome medicine2023
Whole genome sequencing across clinical trials identifies rare coding variants in GPR68 associated with chemotherapy-induced peripheral neuropathy.
Article in Genome medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
What it found
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The trial behind it
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Who cites it
11 citing papers in PubMed, 17 citations in OpenAlex.
- A human iPSC-derived sensory neuron platform for high-throughput discovery of neuroprotectants against chemotherapy-induced peripheral neuropathy.Cell reports. Medicine · 2026Article
- Neuromechanobiology: Bridging Mechanobiology and Neuroscience Through Evidence and Open Questions.Cells · 2026Review
- Celecoxib pretreatment and nab-paclitaxel-associated acute pain syndrome in patients with breast cancer: a prospective, non-randomized controlled clinical study.International journal of surgery (London, England) · 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
- Pharmacogenomics of chemotherapy induced peripheral neuropathy using an electronic health record-derived definition: a genome-wide association study.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2025Article
- G protein-coupled receptors in prostate cancer: research progress and therapeutic targets.Frontiers in cell and developmental biology · 2025Review
- A Suite of Foundation Models Captures the Contextual Interplay Between Codons.bioRxiv : the preprint server for biology · 2024Article
- Recent advances in acid sensing by G protein coupled receptors.Pflugers Archiv : European journal of physiology · 2024Review
- Molecular and modular intricacies of precision oncology.Frontiers in immunology · 2024Review
- Targeting sensory neuron GPCRs for peripheral neuropathic pain.Trends in pharmacological sciences · 2023Review
- 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
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDose-limiting toxicities significantly impact the benefit/risk profile of many drugs. Whole genome sequencing (WGS) in patients receiving drugs with dose-limiting toxicities can identify therapeutic hypotheses to prevent these toxicities. Chemotherapy-induced peripheral neuropathy (CIPN) is a common dose-limiting neurological toxicity of chemotherapies with no effective approach for prevention.
methodsWe conducted a genetic study of time-to-first peripheral neuropathy event using 30× germline WGS data from whole blood samples from 4900 European-ancestry cancer patients in 14 randomized controlled trials. A substantial number of patients in these trials received taxane and platinum-based chemotherapies as part of their treatment regimen, either standard of care or in combination with the PD-L1 inhibitor atezolizumab. The trials spanned several cancers including renal cell carcinoma, triple negative breast cancer, non-small cell lung cancer, small cell lung cancer, bladder cancer, ovarian cancer, and melanoma.
resultsWe identified a locus consisting of low-frequency variants in intron 13 of GRID2 associated with time-to-onset of first peripheral neuropathy (PN) indexed by rs17020773 (p = 2.03 × 10
conclusionsOur genetic study provides insight into the impact of low-frequency and rare coding genetic variation on PN risk and suggests that further study of GPR68 in sensory neurons may yield a therapeutic hypothesis for prevention of CIPN.
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Registered trials
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