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Cellular parameters predictive of the clinical response of colorectal cancers to irinotecan. A preliminary study
Valérie Pavillard1, Virginie Charasson, Audrey Laroche-Clary
1Laboratoire de Pharmacologie des Agents Anticancéreux, Institut Bergonié et Université Victor Segalen Bordeaux 2, 229, cours de l'Argonne 33076 Bordeaux-cedex, France.
Background:
We have examined, in this study, the feasibility of determining cellular factors contributing to irinotecan activity in colorectal cancers. Irinotecan is a camptothecin derivative requiting carboxylesterase activation to SN-38, which interacts with its target enzyme, topoisomerase I.
Materials And Methods:
In 9 surgical or biopsy samples of colorectal tumours and corresponding normal tissue, kept in a tumour bank, we evaluated topoisomerase I expression and activity, respectively by Western blotting and DNA relaxation assay, carboxylesterase activity using two different substrates and p53 status by immunohistochenistry.
Results:
Topoisomerase I expression and activity were significantly correlated, as were the two types of determinations for carboxylesterase activity. Topoisomerase I was significantly more active in tumours than in corresponding normal tissue. The three samples presenting the highest topoisomerase I expression and activity originated from the patients who responded to irinotecan treatment. No such features were apparent for carboxylesterase activity and p53 staining.
Conclusion:
Topoisomerase I expression appeared as the parameter most likely to predict response to irinotecan therapy in the clinical setting.
