ArticlePloS one2015
Association of ABCB1 and FLT3 Polymorphisms with Toxicities and Survival in Asian Patients Receiving Sunitinib for Renal Cell Carcinoma.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 33 citations in OpenAlex.
- Sunitinib as Second-Line Treatment in Advanced Intrahepatic Cholangiocarcinoma: Results From the SUN-CK GERCOR Phase II Trial.Liver international : official journal of the International Association for the Study of the Liver · 2025Trial
- Inter-Ethnic Differences in the Efficacy and Safety of Tyrosine Kinase Inhibitors Used in Oncology: Insights From Phase 3 Clinical Trials.Clinical and translational science · 2025Review
- Computational Analysis of MDR1 Variants Predicts Effect on Cancer Cells via their Effect on mRNA Folding.PLoS computational biology · 2024Article
- FLT3L-dependent dendritic cells control tumor immunity by modulating Treg and NK cell homeostasis.Cell reports. Medicine · 2023Article
- Predictive genomic biomarkers of therapeutic effects in renal cell carcinoma.Cellular oncology (Dordrecht, Netherlands) · 2023Review
- Review
- Genophenotypic Factors and Pharmacogenomics in Adverse Drug Reactions.International journal of molecular sciences · 2021Review
- ABC transporter superfamily. An updated overview, relevance in cancer multidrug resistance and perspectives with personalized medicine.Molecular biology reports · 2021Review
- 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
- Pharmacogenomics to Predict Tumor Therapy Response: A Focus on ATP-Binding Cassette Transporters and Cytochromes P450.Journal of personalized medicine · 2020Review
- The Roles of Common Variation and Somatic Mutation in Cancer Pharmacogenomics.Oncology and therapy · 2019Review
- ATP-Binding Cassette Transporters in the Clinical Implementation of Pharmacogenetics.Journal of personalized medicine · 2018Review
- Article
- 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
14 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sunitinib is a tyrosine kinase inhibitor used as first-line treatment for metastatic renal cell carcinoma (mRCC). Asian ethnicity has been previously associated with lower clearance and greater toxicities for sunitinib treatment, relative to Caucasian ethnicity. Research focusing on identifying corresponding biomarkers of efficacy and toxicity has been hitherto conducted in Caucasian populations, and few of the reported associations have been externally validated. Our work thus aims to investigate candidate biomarkers in Asian patients receiving sunitinib, comparing the observed genotype effects with those reported in Caucasian populations. Using data from 97 Asian mRCC patients treated with sunitinib, we correlated 7 polymorphisms in FLT3, ABCB1, VEGFR2, ABCG2 and BIM with patient toxicities, response, and survival. We observed a stronger association of FLT3 738T genotype with leucopenia in our Asian dataset than that previously reported in Caucasian mRCC patients (odds ratio [OR]=8.0; P=0.03). We observed significant associations of FLT3 738T (OR=2.7), ABCB1 1236T (OR=0.3), ABCB1 3435T (OR=0.1), ABCB1 2677T (OR=0.4), ABCG2 421A (OR=0.3) alleles and ABCB1 3435, 1236, 2677 TTT haplotype (OR=0.1) on neutropenia. Primary resistance (OR=0.1, P=0.004) and inferior survival (progression-free: hazard ratio [HR]=5.5, P=0.001; overall: HR=5.0, P=0.005) were associated with the ABCB1 3435, 1236, 2677 TTT haplotype. In conclusion, ABCB1 and FLT3 polymorphisms may be helpful in predicting sunitinib toxicities, response and survival benefit in Asian mRCC patients. We have also validated the association between FLT3 738T and sunitinib-induced leucopenia previously reported in Caucasian populations, but have not validated other reported genetic associations.
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