Topoisomerases and anthracyclines: Recent advances and perspectives in anticancer therapy and prevention of cardiotoxicity

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22 Citations (Scopus)

Abstract

Topoisomerases are ubiquitous enzymes involved in maintaining genomic stability of the cell by regulating the over- or underwinding of DNA strands. Besides their customary functions, topoisomerases are important cellular targets of widely used anticancer drugs. In particular, topoisomerase IIa (Top2a) has been postulated as the primary molecular target of anthracycline’s anticancer activity, whereas topoisomerase IIß (Top2ß), the only Top2 present in heart tissue, seems to be involved in the development of anthracycline-induced cardiotoxicity. Noteworthy, cardiotoxicity is the most frequent adverse effect of both conventional and modern anticancer targeted therapy, representing the leading noncancer-related cause of morbidity and mortality in long-term survivors. The molecular mechanisms of anthracycline-induced cardiotoxicity have been investigated for decades and, despite the numerous mechanistic hypotheses put forward, its aetiology and pathogenesis still remain controversial. This review is aimed at focusing on the double edge sword of topoisomerase-anthracycline interaction, and, in particular, on the potential role of topoisomerases in anthracyclines anticancer activity as well as in the pathogenesis of anthracycline-induced cardiotoxicity.
Original languageEnglish
Pages (from-to)1607-1626
Number of pages20
JournalCURRENT MEDICINAL CHEMISTRY
Volume24
DOIs
Publication statusPublished - 2017

Keywords

  • Anthracycline
  • Anthracyclines
  • Cancer chemotherapy
  • Cardio-oncology
  • Cardiotoxicity
  • Catalytic inhibitors
  • DNA Repair
  • DNA Topoisomerases
  • DNA Topoisomerases, Type II
  • DNA topoisomerases
  • Heart
  • Humans
  • Molecular Medicine
  • Neoplasms
  • Pharmacology
  • Topoisomerase Inhibitors
  • Topoisomerase poisons

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