ArticleTranslational research : the journal of laboratory and clinical medicine2011
Germline polymorphisms discovered via a cell-based, genome-wide approach predict platinum response in head and neck cancers.
Article in Translational research : the journal of laboratory and clinical medicine, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
35 citing papers in PubMed, 2 syntheses or guidelines pooled it, 48 citations in OpenAlex.
- Genome-wide meta-analysis identifies variants associated with platinating agent susceptibility across populations.The pharmacogenomics journal · 2013Pooled it
- Pooled it
- Article
- Validating methods for testing natural molecules on molecular pathways of interest in silico and in vitro.Journal of preventive medicine and hygiene · 2022Article
- Article
- Extending the lymphoblastoid cell line model for drug combination pharmacogenomics.Pharmacogenomics · 2021Review
- Article
- Exceptional durable response to everolimus in a patient with biphenotypic breast cancer harboring anCold Spring Harbor molecular case studies · 2017Article
- Genetic Variants Contributing to Colistin Cytotoxicity: Identification of TGIF1 and HOXD10 Using a Population Genomics Approach.International journal of molecular sciences · 2017Article
- Clinical Evaluation of Cisplatin Sensitivity of Germline Polymorphisms in Neoadjuvant Chemotherapy for Urothelial Cancer.Clinical genitourinary cancer · 2016Article
- Utility of Lymphoblastoid Cell Lines for Induced Pluripotent Stem Cell Generation.Stem cells international · 2016Article
- Reprogramming LCLs to iPSCs Results in Recovery of Donor-Specific Gene Expression Signature.PLoS genetics · 2015Article
- In vitro human cell line models to predict clinical response to anticancer drugs.Pharmacogenomics · 2015Review
- Integrating cell-based and clinical genome-wide studies to identify genetic variants contributing to treatment failure in neuroblastoma patients.Clinical pharmacology and therapeutics · 2014Article
- Protein quantitative trait loci identify novel candidates modulating cellular response to chemotherapy.PLoS genetics · 2014Article
- Genome-wide association and pharmacological profiling of 29 anticancer agents using lymphoblastoid cell lines.Pharmacogenomics · 2014Article
- Article
- Genetic and epigenetic variants contributing to clofarabine cytotoxicity.Human molecular genetics · 2013Article
- Lymphoblastoid cell lines in pharmacogenomics: how applicable are they to clinical outcomes?Pharmacogenomics · 2013Article
- Integration of cell line and clinical trial genome-wide analyses supports a polygenic architecture of Paclitaxel-induced sensory peripheral neuropathy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2013Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 1 institution in 1 country.
Funding
Abstract
Identifying patients prior to treatment who are more likely to benefit from chemotherapeutic agents or more likely to experience adverse events is an aim of personalized medicine. Pharmacogenomics offers a potential means of achieving this goal through the discovery of predictive germline genetic biomarkers. When applied particularly to the treatment of head and neck cancers, such information could offer significant benefit to patients as a means of potentially reducing morbidity associated with platinum-based chemotherapy. We developed a genome-wide, cell-based approach to identify single nucleotide polymorphisms (SNPs) associated with platinum susceptibility and then evaluated these SNPs as predictors for response and toxicity in head and neck cancer patients treated with platinum-based therapy as part of a phase II clinical trial. Sixty head and neck cancer patients were evaluated. Of 45 genome-wide SNPs examined, we found that 2 SNPs, rs6870861 (P=0.004; false discovery rate [FDR] <0.05) and rs2551038 (P=0.005; FDR <0.05), were associated significantly with overall response to carboplatin-based induction chemotherapy when incorporated into a model along with total carboplatin exposure. Interestingly, these 2 SNPs are associated strongly with the baseline expression of >20 genes (all P ≤10(-4)), and that 2 genes (SLC22A5 and SLCO4C1) are important organic cation/anion transporters known to affect platinum uptake and clearance. Several other SNPs were associated nominally with carboplatin-related hematologic toxicities. These findings demonstrate importantly that a genome-wide, cell-based model can identify novel germline genetic biomarkers of platinum susceptibility, which are replicable in a clinical setting with treated cancer patients and seem clinically meaningful for potentially enabling future personalization of care in such patients.
Indexed as
Identifiers
What OpenQuestion holds
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.