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Updated: Aug 11, 2026

Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms
08:46

Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms

Published on: December 9, 2015

Clinical resistance to topoisomerase-targeted drugs

A M Dingemans1, H M Pinedo, G Giaccone

  • 1Department of Medical Oncology, University Hospital Vrije Universiteit, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands.

Biochimica Et Biophysica Acta
|September 28, 1998
PubMed

Insights

Drug resistance to topoisomerase (topo) inhibitors is complex. While topo expression correlates with sensitivity in vitro, clinical evidence linking topo levels to chemotherapy response remains limited, suggesting multifactorial resistance mechanisms.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • Topoisomerases (topo) are crucial enzymes involved in DNA replication and repair.
  • Topo-mediated drug resistance is a significant challenge in cancer chemotherapy.
  • Understanding topo expression and its role in drug resistance is vital for improving treatment outcomes.

Purpose of the Study:

  • To review topoisomerase-mediated drug resistance and expression in human cancers.
  • To analyze the relationship between topoisomerase expression and sensitivity to topoisomerase inhibitors.
  • To critically evaluate clinical studies on topoisomerase expression and chemotherapy response.

Main Methods:

  • Literature review of in vitro and clinical studies on topoisomerase expression and drug resistance.
  • Analysis of studies investigating topoisomerase I, IIalpha, and IIbeta expression in human tissues and cancers.
  • Examination of factors contributing to drug resistance, including drug transporters and cell cycle regulation.

Main Results:

  • In vitro studies suggest a link between topoisomerase I, IIalpha, or IIbeta expression and sensitivity to inhibitors.
  • Topo IIalpha expression correlates with tumor proliferation, while topo IIbeta is found in both proliferating and quiescent cells.
  • Higher topo I levels are observed in some tumors compared to normal tissues.
  • Reduced topo IIalpha levels may be seen after chemotherapy treatment.
  • No definitive link between topoisomerase gene expression/activity and chemotherapy response has been established in clinical studies.

Conclusions:

  • Topoisomerase-mediated drug resistance is multifactorial, involving transporters and cell cycle regulation.
  • Clinical data on the direct correlation between topoisomerase expression and chemotherapy response is limited.
  • Further well-designed clinical studies are needed to clarify the role of topoisomerases in predicting treatment outcomes.

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