Cellular parameters predictive of the clinical response of colorectal cancers to irinotecan. A preliminary study.

Abstract

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.