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Topoisomerase I activity in squamous cell carcinoma of the head and neck
J S Masin1, S J Berger, S Setrakian
1Department of Otolaryngology-Head and Neck Surgery, Case-Western Reserve University, School of Medicine, Cleveland, OH 44106-4937, USA.
Abstract:
In recent preclinical and clinical trials, topoisomerase I inhibitors have shown great promise as antitumor agents. These agents are most effective against tumors with high topoisomerase I activity. Therefore, determining topoisomerase I activity in advance may predict response to topoisomerase I inhibitors. Squamous cell carcinoma of the head and neck and normal tissue samples were obtained from 12 patients. Cellular extracts were prepared, and topoisomerase I activity assays were performed. The results suggest that topoisomerase I activity in squamous cell carcinoma of the head and neck is increased approximately sixtyfold compared to normal tissue. Increased activity often correlates with clinical responsiveness; these results predict that topoisomerase I inhibitors should be effective and selective against squamous cell carcinoma of the head and neck.
Insights
Topoisomerase I inhibitors show promise against head and neck cancers. This study found significantly higher topoisomerase I activity in these tumors, suggesting these inhibitors could be effective treatments.
Area of Science:
- Oncology
- Biochemistry
- Molecular Biology
Background:
- Topoisomerase I inhibitors are promising antitumor agents, particularly effective against tumors with high enzyme activity.
- Predicting patient response to these inhibitors based on pre-treatment enzyme levels is a key clinical challenge.
Purpose of the Study:
- To investigate and quantify topoisomerase I activity in squamous cell carcinoma of the head and neck (HNSCC) compared to normal tissues.
- To assess the potential of topoisomerase I activity as a predictive biomarker for HNSCC response to topoisomerase I inhibitors.
Main Methods:
- Analysis of topoisomerase I activity in cellular extracts from HNSCC and adjacent normal tissue samples from 12 patients.
- Enzyme activity assays were performed to quantify differences between tumor and normal tissues.
Main Results:
- Topoisomerase I activity was found to be approximately sixtyfold higher in HNSCC samples compared to normal tissue samples.
- Elevated enzyme activity in tumors suggests a potential correlation with clinical responsiveness to targeted therapies.
Conclusions:
- Squamous cell carcinoma of the head and neck exhibits significantly elevated topoisomerase I activity.
- These findings predict that topoisomerase I inhibitors may be effective and selective antitumor agents for HNSCC.