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Régulation de l'inactivation intratumorale de l'agent antinéoplasique irinotécan par un mécanisme épigénétique

by Gagnon, Jean-François

Abstract (Summary)
UGT1A1 is the main enzyme involved in the hepatic and tumoral inactivation of SN-38, an anticancer agent used in first line treatment of metastasic colorectal cancer. UGT1A1 genetic factors determine response to irinotecan therapy. We hypothesised that an epigenetic mechanism, more specifically methylation, is involved in tumoral regulation of UGT1A1 levels. Specific CpG islands in the UGT1A1 gene are hypermethylated and linked to the repression of gene expression and to lower levels of SN-38 glucuronidation in colon tumor cells in vitro. In addition, methylation of specific CpG was linked to lower expression of UGT1A1 gene in primary colon tumors from patients. Our data support that methylation profile of the UGT1A1 gene determine SN-38 tumoral concentration and may help to predict tumoral response to irinotecan.
This document abstract is also available in French.
Bibliographical Information:

Advisor:Guillemette, Chantal

School:Université Laval

School Location:Canada - Quebec / Québec

Source Type:Master's Thesis

Keywords:pharmacie

ISBN:

Date of Publication:09/01/2005

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