title: Topoisomerases and Anthracyclines: Recent Advances and Perspectives in Anticancer Therapy and Prevention of Cardiotoxicity.
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.
authors.affiliation: Institute of Biochemistry and Clinical Biochemistry, School of Medicine, Catholic University, Largo F. Vito 1, 00168, Rome. Italy.
authors.forename: Alvaro
authors.initials: A
authors.lastname: Mordente
authors.affiliation: Institute of Biochemistry and Clinical Biochemistry, School of Medicine, Catholic University, Largo F. Vito 1, 00168, Rome. Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Meucci
authors.affiliation: Institute of Biochemistry and Clinical Biochemistry, School of Medicine, Catholic University, Largo F. Vito 1, 00168, Rome. Italy.
authors.forename: Giuseppe Ettore
authors.initials: GE
authors.lastname: Martorana
authors.affiliation: Laboratory of Cellular Biochemistry and Molecular Biology, CriBeNS, Catholic University, Largo A. Gemelli, 1, 20123, Milan. Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Tavian
authors.affiliation: Institute of Biochemistry and Clinical Biochemistry, School of Medicine, Catholic University, Largo F. Vito 1, 00168, Rome. Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Silvestrini
mesh_terms: D018943:Anthracyclines / Q000737:chemistry / Q000627:therapeutic use / Q000633:toxicity*; D004260:DNA Repair / Q000187:drug effects; D026942:DNA Topoisomerases / Q000737:chemistry / Q000378:metabolism*; D004250:DNA Topoisomerases, Type II / Q000737:chemistry / Q000378:metabolism; D006321:Heart / Q000187:drug effects*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D059003:Topoisomerase Inhibitors / Q000737:chemistry / Q000627:therapeutic use / Q000633:toxicity*
chemical_list: D018943:Anthracyclines; D059003:Topoisomerase Inhibitors; D026942:DNA Topoisomerases; D004250:DNA Topoisomerases, Type II
keywords: Anthracycline; DNA topoisomerases; cancer chemotherapy; cardio-oncology; cardiotoxicity; catalytic inhibitors; topoisomerase poisons