Topoisomerases and Anthracyclines: Recent Advances and Perspectives in Anticancer Therapy and Prevention of Cardiotoxicity

Alvaro Mordente, Elisabetta Meucci Calabrese, Giuseppe Ettore Martorana, Daniela Tavian, Andrea Silvestrini

Risultato della ricerca: Contributo in rivistaArticolo in rivistapeer review

22 Citazioni (Scopus)


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 II β (Top2β), the only Top2 present in heart tissue, seems to be involved into 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.
Lingua originaleEnglish
pagine (da-a)1607-1626
Numero di pagine24
RivistaCurrent Medicinal Chemistry
Stato di pubblicazionePubblicato - 2017


  • topoisomerases


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