ArticleEuropean urology focus2016
Pharmacogenomic Markers of Targeted Therapy Toxicity in Patients with Metastatic Renal Cell Carcinoma.
Article in European urology focus, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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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.
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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
7 citing papers in PubMed, 13 citations in OpenAlex.
- Three Layers of Personalized Medicine in the Use of Sirolimus and Its Derivatives for the Treatment of Cancer.Journal of personalized medicine · 2023Review
- Meta-Analysis of ABCG2 and ABCB1 Polymorphisms With Sunitinib-Induced Toxicity and Efficacy in Renal Cell Carcinoma.Frontiers in pharmacology · 2021Article
- Pharmacogenetics for severe adverse drug reactions induced by molecular-targeted therapy.Cancer science · 2020Review
- The pan-cancer landscape of prognostic germline variants in 10,582 patients.Genome medicine · 2020Article
- Article
- Cytochromes P450 1A2 and 3A4 Catalyze the Metabolic Activation of Sunitinib.Chemical research in toxicology · 2018Article
- Genetic polymorphisms associated with adverse reactions of molecular-targeted therapies in renal cell carcinoma.Medical oncology (Northwood, London, England) · 2018Review
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 3 countries.
Funding
Abstract
backgroundTargeted therapy (TT) in metastatic renal cell carcinoma (mRCC) may be associated with a high rate of toxicity that undermines treatment efficacy and patient quality of life. Polymorphisms in genes involved in the pharmacokinetic pathways of TTs may predict toxicity.
objectiveTo investigate whether selected single-nucleotide polymorphisms (SNPs) in three core genes involved in the metabolism and transport of sunitinib and the mTOR inhibitors everolimus and temsirolimus are associated with adverse events (AEs). DESIGN, SETTING, AND
participantsGermline DNA was extracted from blood or normal kidney tissue from mRCC patients of Caucasian ethnicity in two cohorts treated with either sunitinib (n=159) or mTOR inhibitors (n=62). Six SNPs in three candidate genes (CYP3A4: rs2242480, rs4646437, and rs2246709; CYP3A5: rs15524; and ABCB1: rs2032582 and rs1045642) were analyzed. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary endpoints were grade ≥3 AEs for all patients; grade ≥3 hypertension in the sunitinib cohort, and any grade pneumonitis in the mTOR inhibitors cohort. A logistic regression model was used to assess the association between SNPs and AEs, with adjustment for relevant clinical factors. RESULTS AND LIMITATIONS: In total, 221 samples were successfully genotyped for the selected SNPs. In the sunitinib cohort, the CYP3A4 rs464637 AG variant was associated with a lower risk of high-grade AEs (odds ratio 0.27, 95% confidence interval 0.08-0.88; p=0.03), but no SNPs were associated with hypertension. In the mTOR inhibitor cohort, none of the selected SNPs was associated with analyzed toxicities.
conclusionsWe observed an association between CYP3A4 polymorphisms and toxicity outcomes in mRCC patients treated with sunitinib, but not with everolimus or temsirolimus. Our findings are exploratory in nature, and further validation in independent and larger cohorts is needed. PATIENT SUMMARY: We found that variants of CYP3A4, a gene involved in drug metabolism, are associated with sunitinib toxicity. This information may help in better selection of patients for targeted therapies in metastatic renal cell carcinoma.
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