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 IIα (Top2α) has been postulated as the primary molecular target of anthracycline’s anticancer activity, whereas topoisomerase IIβ (Top2β), 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 anthracyclineinduced 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.Keywords: Anthracycline, cancer chemotherapy, cardio-oncology, cardiotoxicity, catalytic inhibitors, DNA topoisomerases, topoisomerase poisons.
Current Medicinal Chemistry
Title:Topoisomerases and Anthracyclines: Recent Advances and Perspectives in Anticancer Therapy and Prevention of Cardiotoxicity
Volume: 24 Issue: 15
Author(s): Alvaro Mordente*, Elisabetta Meucci, Giuseppe Ettore Martorana, Daniela Tavian and Andrea Silvestrini*
Affiliation:
- Institute of Biochemistry and Clinical Biochemistry, School of Medicine, Catholic University, Largo F. Vito 1, 00168, Rome,Italy
- Institute of Biochemistry and Clinical Biochemistry, School of Medicine, Catholic University, Largo F. Vito 1, 00168, Rome,Italy
Keywords: Anthracycline, cancer chemotherapy, cardio-oncology, cardiotoxicity, catalytic inhibitors, DNA topoisomerases, topoisomerase poisons.
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 IIα (Top2α) has been postulated as the primary molecular target of anthracycline’s anticancer activity, whereas topoisomerase IIβ (Top2β), 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 anthracyclineinduced 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.Export Options
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Cite this article as:
Mordente Alvaro*, Meucci Elisabetta, Martorana Ettore Giuseppe, Tavian Daniela and Silvestrini Andrea*, Topoisomerases and Anthracyclines: Recent Advances and Perspectives in Anticancer Therapy and Prevention of Cardiotoxicity, Current Medicinal Chemistry 2017; 24 (15) . https://dx.doi.org/10.2174/0929867323666161214120355
DOI https://dx.doi.org/10.2174/0929867323666161214120355 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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