title: From Molecular Mechanisms to Clinical Management of Antineoplastic Drug-Induced Cardiovascular Toxicity: A Translational Overview.
abstract: Significance:Antineoplastic therapies have significantly improved the prognosis of oncology patients. However, these treatments can bring to a higher incidence of side-effects, including the worrying cardiovascular toxicity (CTX).Recent Advances:Substantial evidence indicates multiple mechanisms of CTX, with redox mechanisms playing a key role. Recent data singled out mitochondria as key targets for antineoplastic drug-induced CTX; understanding the underlying mechanisms is, therefore, crucial for effective cardioprotection, without compromising the efficacy of anti-cancer treatments.Critical Issues:CTX can occur within a few days or many years after treatment. Type I CTX is associated with irreversible cardiac cell injury, and it is typically caused by anthracyclines and traditional chemotherapeutics. Type II CTX is generally caused by novel biologics and more targeted drugs, and it is associated with reversible myocardial dysfunction. Therefore, patients undergoing anti-cancer treatments should be closely monitored, and patients at risk of CTX should be identified before beginning treatment to reduce CTX-related morbidity.Future Directions:Genetic profiling of clinical risk factors and an integrated approach using molecular, imaging, and clinical data may allow the recognition of patients who are at a high risk of developing chemotherapy-related CTX, and it may suggest methodologies to limit damage in a wider range of patients. The involvement of redox mechanisms in cancer biology and anticancer treatments is a very active field of research. Further investigations will be necessary to uncover the hallmarks of cancer from a redox perspective and to develop more efficacious antineoplastic therapies that also spare the cardiovascular system.
authors.affiliation: 1 Department of Translational Medical Sciences, Federico II University, Naples, Italy.
authors.forename: Carlo Gabriele
authors.initials: CG
authors.lastname: Tocchetti
authors.affiliation: 2 Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy.
authors.forename: Christian
authors.initials: C
authors.lastname: Cadeddu
authors.affiliation: 3 Biomedical Department of Internal Medicine, University of Palermo, Palermo, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Di Lisi
authors.affiliation: 4 Department of Clinical and Biological Sciences, University of Turin, Turin, Italy.
authors.forename: Saveria
authors.initials: S
authors.lastname: Femminò
authors.affiliation: 5 Center of Aging Sciences and Translational Medicine - CESI-MeT, "G. d'Annunzio" University, Chieti, Italy.|6 Department of Internal Medicine, The Texas Heart Institute and Center for Cardiovascular Biology and Atherosclerosis Research, The University of Texas Health Science Center at Houston, Houston, Texas.
authors.forename: Rosalinda
authors.initials: R
authors.lastname: Madonna
authors.affiliation: 7 Cardiology Unit, Emergency Department, University Hospital of Ferrara, Ferrara, Italy.
authors.forename: Donato
authors.initials: D
authors.lastname: Mele
authors.affiliation: 8 Department of General Surgery and Medical-Surgery Specialities, University of Catania, Catania, Italy.
authors.forename: Ines
authors.initials: I
authors.lastname: Monte
authors.affiliation: 3 Biomedical Department of Internal Medicine, University of Palermo, Palermo, Italy.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Novo
authors.affiliation: 4 Department of Clinical and Biological Sciences, University of Turin, Turin, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Penna
authors.affiliation: 9 U.O.C. Magnetic Resonance Imaging, Fondazione Toscana G. Monasterio C.N.R., Pisa, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Pepe
authors.affiliation: 10 Clinic of Cardiovascular Diseases, IRCCS San Martino IST, Genova, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Spallarossa
authors.affiliation: 1 Department of Translational Medical Sciences, Federico II University, Naples, Italy.|11 Center for Basic and Clinical Immunology Research (CISI) - Federico II University, Naples, Italy.
authors.forename: Gilda
authors.initials: G
authors.lastname: Varricchi
authors.affiliation: 12 Division of Cardiology, Clinical and Experimental Department of Medicine and Pharmacology, Policlinico "G. Martino" University of Messina, Messina, Italy.
authors.forename: Concetta
authors.initials: C
authors.lastname: Zito
authors.affiliation: 4 Department of Clinical and Biological Sciences, University of Turin, Turin, Italy.
authors.forename: Pasquale
authors.initials: P
authors.lastname: Pagliaro
authors.affiliation: 2 Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Mercuro
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000494:pharmacology; D066126:Cardiotoxicity / Q000209:etiology / Q000378:metabolism*; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D010084:Oxidation-Reduction
chemical_list: D000970:Antineoplastic Agents
keywords: ErbB2 inhibitors; cancer immunotherapy; chemotherapy; oxidative/nitrosative stress; tyrosine kinase inhibitors; vascular endothelial growth factor