title: Mechanisms and management of doxorubicin cardiotoxicity.
abstract: Doxorubicin is an effective anti-tumor agent with a cumulative dose-dependent cardiotoxicity. In addition to its principal toxic mechanisms involving iron and redox reactions, recent studies have described new mechanisms of doxorubicin-induced cell death, including abnormal protein processing, hyper-activated innate immune responses, inhibition of neuregulin-1 (NRG1)/ErbB(HER) signalling, impaired progenitor cell renewal/cardiac repair, and decreased vasculogenesis. Although multiple mechanisms involved in doxorubicin cardiotoxicity have been studied, there is presently no clinically proven treatment established for doxorubicin cardiomyopathy. Iron chelator dexrazoxane, angiotensin converting enzyme (ACE) inhibitors, and β-blockade have been proposed as potential preventive strategies for doxorubicin cardiotoxicity. Novel approaches such as anti-miR-146 or recombinant NRG1 to increase cardiomyocyte resistance to toxicity may be of interest in the future.
authors.affiliation: Division of Cardiology, Heart and Stroke/Richard Lewar Centre of Excellence, University Health Network, University of Toronto, Toronto General Hospital, Ontario, Canada.
authors.forename: Y
authors.initials: Y
authors.lastname: Shi
authors.forename: M
authors.initials: M
authors.lastname: Moon
authors.forename: S
authors.initials: S
authors.lastname: Dawood
authors.forename: B
authors.initials: B
authors.lastname: McManus
authors.forename: P P
authors.initials: PP
authors.lastname: Liu
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000009:adverse effects; D009202:Cardiomyopathies / Q000139:chemically induced* / Q000175:diagnosis / Q000517:prevention & control*; D054715:Cardiotoxins / Q000009:adverse effects*; D004317:Doxorubicin / Q000009:adverse effects*; D006801:Humans
chemical_list: D000903:Antibiotics, Antineoplastic; D054715:Cardiotoxins; D004317:Doxorubicin