Journal article
Pregnane x Receptor (PXR) expression in colorectal cancer cells restricts irinotecan chemosensitivity through enhanced SN-38 glucuronidation
Caroline Raynal, Jean-Marc Pascussi, Geraldine Legueline, Cyril Breuker, Jovana Kantar, Benjamin Lallemant, Sylvain Poujol, Caroline Bonnans, Dominique Joubert, Frederic Hollande, Serge Lumbroso, Jean-Paul Brouillet, Alexandre Evrard
MOLECULAR CANCER | BMC | Published : 2010
Open access
Abstract
Clinical efficacy of chemotherapy in colorectal cancer is subjected to broad inter-individual variations leading to the inability to predict outcome and toxicity. The topoisomerase I inhibitor irinotecan (CPT-11) is worldwide approved for the treatment of metastatic colorectal cancer and undergoes extensive peripheral and tumoral metabolism. PXR is a xenoreceptor activated by many drugs and environmental compounds regulating the expression of drug metabolism and transport genes in detoxification organs such as liver and gastrointestinal tract. Considering the metabolic pathway of irinotecan and the tissue distribution of Pregnane x Receptor (PXR), we hypothesized that PXR could play a key ro..
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Funding Acknowledgements
This work was funded by La Ligue contre le Cancer, Universite Montpellier I and CHU Nimes. We thank Jean-Francois Bourgaux, Christine Pignodel, Julie Pannequin for providing us colon tissues, Celia Basurko for statistical analysis and Francoise Malosse for helpful technical assistance for HPLC analysis.