Tyrosyl-DNA phosphodiesterase 1 targeting for modulation of camptothecin-based treatment

G. L. Beretta, G. Cossa, L. Gatti, F. Zunino, P. Perego

Research output: Contribution to journalArticlepeer-review

Abstract

The targeting of specific DNA repair mechanisms may be a promising strategy to improve the efficacy of antitumor therapy. The cytotoxic effects of the clinically relevant topoisomerase 1 (Top1) poison camptothecins are related to the generation of DNA lesions and tumor cells may be resistant to DNA damaging agents due to increased repair. Tyrosyl-DNA phosphodiesterase 1 (TDP1) is implicated in the repair of strand breaks by removing abortive Top1/DNA complexes. Thus, a role for TDP1 in counteracting DNA damage induced by camptothecins has been proposed. Here, we review the role of TDP1 in DNA repair with particular reference to TDP1 function, its cooperation with other pathways and the development of pharmacological inhibitors.

Original languageEnglish
Pages (from-to)1500-1508
Number of pages9
JournalCurrent Medicinal Chemistry
Volume17
Issue number15
DOIs
Publication statusPublished - 2010

Keywords

  • Camptothecin
  • DNA repair pathways
  • Drug resistance
  • SCAN-1
  • Topoisomerase 1
  • Tyrosyl-DNA phosphodiesterase 1

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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