Targeting topoisomerase I: Molecular mechanisms and cellular determinants of response to topoisomerase I inhibitors

Giovanni Luca Beretta, Paola Perego, Franco Zunino

Research output: Contribution to journalArticle

Abstract

Background: Topoisomerase I is required for DNA relaxation during critical cellular functions. The identification of camptothecins as specific enzyme inhibitors and their clinical efficacy have stimulated extensive efforts to exploit topoisomerase I as a tumor target and explain the putative mechanisms of antitumor-specific action. Objective: This review provides an overview of the recent achievements in the development of topoisomerase I inhibitors and in the explanation of the biological pathways involved in tumor response. Results/conclusion: In spite of the difficulty to identify novel topoisomerase I inhibitors with improved pharmacological properties, a growing body of evidence supports the possibility of optimizing the therapeutic profile of available agents. The explanation of defense mechanisms and the molecular determinants of tumor cell response is expected to provide a basis for the design of combination approaches for optimization of topoisomerase I inhibitors-based therapy.

Original languageEnglish
Pages (from-to)1243-1256
Number of pages14
JournalExpert Opinion on Therapeutic Targets
Volume12
Issue number10
DOIs
Publication statusPublished - Oct 2008

Keywords

  • Apoptosis
  • Camptothecins
  • Cleavable complex
  • DNA damage
  • Topoisomerase I

ASJC Scopus subject areas

  • Drug Discovery
  • Pharmacology
  • Clinical Biochemistry
  • Molecular Medicine

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