title: Pathophysiology of cardiotoxicity from target therapy and angiogenesis inhibitors.
abstract: The progress in cancer therapy and the increase in number of long-term survivors reveal the issue of cardiovascular side-effects of anticancer drugs. Cardiotoxicity has become a significant problem, and the risks of adverse cardiac events induced by systemic drugs need to be seriously considered. Potential cardiovascular toxicities linked to anticancer agents include arrhythmias, myocardial ischemia and infarction, hypertension, thromboembolism, left ventricular dysfunction, and heart failure. It has been shown that several anticancer drugs seriously affect the cardiovascular system, such as ErbB2 inhibitors, vascular endothelial growth factor (VEGF) inhibitors, multitargeted kinase inhibitors, Abelson murine leukemia viral oncogene homolog inhibitors, and others. Each of these agents has a different mechanism through which it affects the cardiovascular system. ErbB2 inhibitors block the ErbB4/ErbB2 heterodimerization pathway triggered by Neuregulin-1, which is essential for cardiomyocyte survival. VEGF signaling is crucial for vascular growth, but it also has a major impact on myocardial function, and the VEGF pathway is also essential for maintenance of cardiovascular homeostasis. Drugs that inhibit the VEGF signaling pathway lead to a net reduction in capillary density and loss of contractile function. Here, we review the mechanisms and pathophysiology of the most significant cardiotoxic effects of ErbB2 inhibitors and antiangiogenic drugs. Moreover, we highlight the role of cardioncology in recognizing these toxicities, developing strategies to prevent or minimize cardiovascular toxicity, and reducing long-term cardiotoxic effects.
authors.affiliation: aDivision of Cardiology, Istituto Nazionale per lo Studio e la Cura dei Tumor 'Fondazione Giovanni Pascale' - IRCCS bCEINGE Biotecnologie Avanzate S.C.A.R.L cDepartment of Breast Surgery and Cancer Prevention, Istituto Nazionale per lo Studio e la Cura dei Tumori 'Fondazione Giovanni Pascale' - IRCCS dDepartment of Molecular Medicine and Medical Biotechnology, University 'Federico II' eDepartment of Senology, Division of Breast Oncology Istituto Nazionale per lo Studio e la Cura dei Tumori 'Fondazione Giovanni Pascale' - IRCCS, Naples fClinic of Cardiovascular Diseases, IRCCS San Martino IST, Genoa gDepartment of Medical Sciences 'Mario Aresu', University of Cagliari, Cagliari, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Maurea
authors.forename: Carmela
authors.initials: C
authors.lastname: Coppola
authors.forename: Giovanna
authors.initials: G
authors.lastname: Piscopo
authors.forename: Francesca
authors.initials: F
authors.lastname: Galletta
authors.forename: Gennaro
authors.initials: G
authors.lastname: Riccio
authors.forename: Emanuela
authors.initials: E
authors.lastname: Esposito
authors.forename: Claudia
authors.initials: C
authors.lastname: De Lorenzo
authors.forename: Michelino
authors.initials: M
authors.lastname: De Laurentiis
authors.forename: Paolo
authors.initials: P
authors.lastname: Spallarossa
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Mercuro
mesh_terms: D020533:Angiogenesis Inhibitors / Q000009:adverse effects*; D000911:Antibodies, Monoclonal / Q000009:adverse effects; D066126:Cardiotoxicity / Q000503:physiopathology; D002318:Cardiovascular Diseases / Q000139:chemically induced* / Q000517:prevention & control; D006321:Heart / Q000187:drug effects / Q000503:physiopathology*; D006801:Humans; D058990:Molecular Targeted Therapy / Q000009:adverse effects*; D009369:Neoplasms / Q000188:drug therapy; D061988:Proteasome Inhibitors / Q000009:adverse effects; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors; D042442:Vascular Endothelial Growth Factors / Q000009:adverse effects
chemical_list: D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061988:Proteasome Inhibitors; D018719:Erb-b2 Receptor Tyrosine Kinases; D042442:Vascular Endothelial Growth Factors