title: Anthracycline cardiotoxicity.
abstract: BACKGROUND
  Anthracyclines are widely prescribed anticancer agents that cause a dose-related cardiotoxicity, often aggravated by nonanthracycline chemotherapeutics or new generation targeted drugs. Anthracycline cardiotoxicity may occur anytime in the life of cancer survivors. Understanding the molecular mechanisms and clinical correlates of cardiotoxicity is necessary to improve the therapeutic index of anthracyclines or to identify active, but less cardiotoxic analogs.
  
  
  METHODS
  The authors review the pharmacokinetic, pharmacodynamic and biochemical mechanisms of anthracycline cardiotoxicity and correlate them to clinical phenotypes of cardiac dysfunction. Attention is paid to bioactivation mechanisms that converted anthracyclines to reactive oxygen species (ROS) or long-lived secondary alcohol metabolites. Preclinical aspects and clinical implications of the "oxidative stress" or "secondary alcohol metabolite" hypotheses are discussed on the basis of literature that cuts across bench and evidence-based medicine. Interactions of anthracyclines with comorbidities or unfavorable lifestyle choices were identified as important cofactors of the lifetime risk of cardiotoxicity and as possible targets of preventative strategies.
  
  
  CONCLUSIONS
  Anthracycline cardiotoxicity is a multifactorial process that needs to be incorporated in a translational framework, where individual genetic background, comorbidities, lifestyles and other drugs play an equally important role. Fears for cardiotoxicity should not discourage from using anthracyclines in many oncologic settings. Cardioprotective strategies are available and should be used more pragmatically in routine clinical practice.
authors.affiliation: Campus Bio-Medico University Hospital, CIR and Drug Sciences, Via Alvaro del Portillo, 21, 00128 Rome, Italy.
authors.forename: Pierantonio
authors.initials: P
authors.lastname: Menna
authors.forename: Odalys Gonzalez
authors.initials: OG
authors.lastname: Paz
authors.forename: Massimo
authors.initials: M
authors.lastname: Chello
authors.forename: Elvio
authors.initials: E
authors.lastname: Covino
authors.forename: Emanuela
authors.initials: E
authors.lastname: Salvatorelli
authors.forename: Giorgio
authors.initials: G
authors.lastname: Minotti
mesh_terms: D000438:Alcohols / Q000378:metabolism; D000818:Animals; D018943:Anthracyclines / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D006331:Heart Diseases / Q000139:chemically induced* / Q000517:prevention & control; D006801:Humans; D008019:Life Style; D009369:Neoplasms / Q000188:drug therapy; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D012307:Risk Factors
chemical_list: D000438:Alcohols; D018943:Anthracyclines; D000970:Antineoplastic Agents; D017382:Reactive Oxygen Species