Topoisomerase I inhibition in colorectal cancer: biomarkers and therapeutic targets

Br J Cancer. 2012 Jan 3;106(1):18-24. doi: 10.1038/bjc.2011.498. Epub 2011 Nov 22.


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.

Publication types

  • Review

MeSH terms

  • Biomarkers, Tumor / metabolism*
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / metabolism
  • Humans
  • Topoisomerase I Inhibitors / therapeutic use*


  • Biomarkers, Tumor
  • Topoisomerase I Inhibitors