Topoisomerase I inhibition in colorectal cancer: biomarkers and therapeutic targets

Gilbert, D.C., Chalmers, A.J. and El-Khamisy, S.F. (2012) Topoisomerase I inhibition in colorectal cancer: biomarkers and therapeutic targets. British Journal of Cancer, 106(1), pp. 18-24. (doi: 10.1038/bjc.2011.498)

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The topoisomerase I (Top 1) poison irinotecan is an important component of the modern treatment of colorectal cancer. By stabilising Top 1-DNA complexes, irinotecan generates Top 1-linked DNA single-strand breaks that can evolve into double-strand breaks and ultimately cause cell death. However, cancer cells may overcome cell killing by releasing the stalled topoisomerase from DNA termini, thereby reducing the efficacy of Top 1 poisons in clinics. Thus, understanding the DNA repair mechanisms involved in the repair of Top 1-mediated DNA damage provides a useful tool to identify potential biomarkers that predict response to this class of chemotherapy. Furthermore, targeting these pathways could enhance the therapeutic benefits of Top 1 poisons. In this review, we describe the cellular mechanisms and consequences of targeting Top 1 activity in cells. We summarise preclinical data and discuss the potential clinical utility of small-molecule inhibitors of the key proteins.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Chalmers, Professor Anthony
Authors: Gilbert, D.C., Chalmers, A.J., and El-Khamisy, S.F.
College/School:College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing > Clinical Specialities
Journal Name:British Journal of Cancer
Published Online:22 November 2011

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