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Current Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Tyrosyl-DNA Phosphodiesterase 1 Targeting for Modulation of Camptothecin-Based Treatment

Author(s): G. L. Beretta, G. Cossa, L. Gatti, F. Zunino and P. Perego

Volume 17 , Issue 15 , 2010

Page: [1500 - 1508] Pages: 9

DOI: 10.2174/092986710790979971

Price: $65

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.

Keywords: Tyrosyl-DNA phosphodiesterase 1, topoisomerase 1, SCAN-1, camptothecin, DNA repair pathways, drug resistance


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