Journal article
Polymorphisms in cytochromes P450 2C8 and 3A5 are associated with paclitaxel neurotoxicity
S Leskelä, C Jara, LJ Leandro-García, A Martínez, J García-Donas, S Hernando, A Hurtado, JCC Vicario, C Montero-Conde, I Landa, E López-Jiménez, A Cascón, RL Milne, M Robledo, C Rodríguez-Antona
Pharmacogenomics Journal | Published : 2011
DOI: 10.1038/tpj.2010.13
Abstract
Neurotoxicity is one of the most relevant dose-limiting toxicities of the anticancer drug paclitaxel. It exhibits substantial interindividual variability of unknown molecular basis, and represents one of the major challenges for the improvement of paclitaxel therapy. The extensive variability in paclitaxel clearance and metabolism lead us to investigate the association between polymorphisms in paclitaxel elimination pathway and neurotoxicity. We selected 13 relevant polymorphisms in genes encoding paclitaxel metabolizing enzymes (CYP2C8, CYP3A4 and CYP3A5) and transporters (organic anion transporting polypeptide (OATP) 1B1, OATP1B3 and P-glycoprotein) and genotyped them in 118 Spanish cancer..
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Awarded by Fundación Ramón Areces
Funding Acknowledgements
We acknowledge the invaluable help of the Clinical Trials Coordinators Rut Villafane and Teresa Garcia-Donas at the Hospital Alcorcon. This work was supported by projects from the Fundacion Ramon Areces, the Spanish Ministry of Science and Technology (SAF 2006-01139) and the 'Ramon y Cajal' programme. Susanna Leskela has a fellowship from the Spanish Ministry of Education and Science (AP2005-4514).