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Topoisomerase I and II activity in human breast, cervix, lung and colon cancer
H L McLeod1, F Douglas, M Oates
1CRC Department of Medical Oncology, University of Glasgow, The Netherlands.
Abstract:
The identification of human DNA topoisomerases as cellular targets for active anti-cancer drugs has stimulated further interest in topoisomerase function in tumour biology. Topoisomerase I and II catalytic activity is detectable in many normal and malignant tissues. However, little is known about the expression of topoisomerases in most human solid tumours. The present study evaluated topoisomerase I and II activity in biopsy samples from 86 patients with breast, lung, cervix or colon cancers. Significant intra- and inter-tumour variation in topoisomerase expression was observed. Topoisomerase I activity was relatively high in cervix and colon tumours in comparison to lung and breast cancers. Topoisomerase II activity was high in cervix, colon and lung cancers relative to breast cancer. Topoisomerase I and II activity co-segregated in individual colon tumour samples, but no correlation was observed in cervix, lung or breast tumours. The large heterogeneity in both topoisomerase I and II activity within a tumour type suggests a mechanism for variable response to topoisomerase-directed therapy. The differences in activity between tumour groups suggest that the potential efficacy of inhibitors of topoisomerase I in colon and cervical tumours may be greater than in lung and breast tumours. Future in vivo evaluation is required to establish the clinical relevance of the observed heterogeneity in topoisomerase activity.
Insights
This study measured DNA topoisomerase I and II activity in various cancers. Enzyme activity varied significantly between and within tumors, impacting potential anti-cancer drug efficacy.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Human DNA topoisomerases are key targets for anti-cancer drugs.
- Topoisomerase I and II activity is present in normal and malignant tissues.
- Limited data exists on topoisomerase expression in human solid tumors.
Purpose of the Study:
- To evaluate topoisomerase I and II activity in breast, lung, cervix, and colon cancers.
- To investigate the correlation between topoisomerase activity and tumor type.
- To understand the implications of topoisomerase heterogeneity for anti-cancer therapy.
Main Methods:
- Analysis of topoisomerase I and II activity in biopsy samples from 86 cancer patients.
- Comparison of enzyme activity across different tumor types (breast, lung, cervix, colon).
- Assessment of intra- and inter-tumour variation in topoisomerase expression.
Main Results:
- Significant intra- and inter-tumour variation in topoisomerase I and II activity observed.
- Topoisomerase I activity was higher in cervix and colon cancers than in lung and breast cancers.
- Topoisomerase II activity was higher in cervix, colon, and lung cancers than in breast cancer.
- Topoisomerase I and II activity co-segregated in colon tumors but not in others.
- Heterogeneity suggests variable responses to topoisomerase-targeted therapies.
Conclusions:
- Tumour-specific differences in topoisomerase activity may influence the efficacy of related drugs.
- Cervix and colon tumors might respond better to topoisomerase I inhibitors than lung and breast tumors.
- Further in vivo studies are needed to confirm the clinical relevance of observed topoisomerase heterogeneity.