AI Article Synopsis
- The study explores the link between genetic variations (SNPs) in specific genes related to the gemcitabine pathway and the drug's pharmacokinetics in solid tumor patients.
- Significant associations were found between gemcitabine clearance and SNPs in the NT5C2 gene, as well as impacts of other gene SNPs (CDA, SLC29A1) on the clearance of gemcitabine metabolites.
- Findings suggest that understanding these genetic variations could help tailor gemcitabine treatment for individual patients, potentially improving therapy outcomes in solid tumor cases.
Article Abstract
Aim: The aim of this study was to evaluate the association of gemcitabine pathway SNPs with detailed pharmacokinetic measures obtained from solid tumor patients receiving gemcitabine-based therapy.
Materials & Methods: SNPs within nine gemcitabine pathway genes, namely CDA, CMPK, DCK, DCTD, NT5C2, NT5C3, SLC28A1, SLC28A3 and SLC29A1 were analyzed for association with gemcitabine pharmacokinetics.
Results: Significant association of gemcitabine clearance with SNPs in NT5C2 was identified. Clearance of 2´,2´-difluorodeoxyuridine, a gemcitabine metabolite was significantly predicted by CDA, SLC29A1 and NT5C2 SNPs. This study reports an association of formation clearance of 2´,2´-difluoro-2´-deoxycytidine triphosphate, an active form of gemcitabine with SNPs within uptake transporters SLC28A1, SLC28A3 and SLC29A1.
Conclusion: Genetic variation in gemcitabine pathway genes is associated with its pharmacokinetics and hence could influence gemcitabine response. Our study identified pharmacogenetic markers that could be further tested in larger patient cohorts and could open up opportunities to individualize therapy in solid tumor patients.
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| http://dx.doi.org/10.2217/pgs.12.81 | DOI Listing |
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