title: Vascular Toxicities of Cancer Therapies: The Old and the New--An Evolving Avenue.
abstract: Since the late 1990s, there has been a steady decline in cancer-related mortality, in part related to the introduction of so-called targeted therapies. Intended to interfere with a specific molecular pathway, these therapies have, paradoxically, led to a number of effects off their intended cancer tissue or molecular targets. The latest examples are tyrosine kinase inhibitors targeting the Philadelphia Chromosome mutation product, which have been associated with progressive atherosclerosis and acute vascular events. In addition, agents designed to interfere with the vascular growth factor signaling pathway have vascular side effects ranging from hypertension to arterial events and cardiomyocyte toxicity. Interestingly, the risk of cardiotoxicity with drugs such as trastuzumab is predicted by preexisting cardiovascular risk factors and disease, posing the question of a vascular component to the pathophysiology. The effect on the coronary circulation has been the leading explanation for the cardiotoxicity of 5-fluorouracil and may be the underlying the mechanism of presentation of apical ballooning syndrome with various chemotherapeutic agents. Classical chemotherapeutic agents such as cisplatin, often used in combination with bleomycin and vinca alkaloids, can lead to vascular events including acute coronary thrombosis and may be associated with an increased long-term cardiovascular risk. This review is intended to provide an update on the evolving spectrum of vascular toxicities with cancer therapeutics, particularly as they pertain to clinical practice, and to the conceptualization of cardiovascular diseases, as well. Vascular toxicity with cancer therapy: the old and the new, an evolving avenue.
authors.affiliation: From Mayo Clinic, Division of Cardiovascular Diseases, Rochester, MN (J.H.); University of California at Los Angeles, Division of Cardiology, Los Angeles (E.-H.Y.); University of Texas, MD Anderson Cancer Center, Houston (C.A.I.); Arkansas Heart Hospital, Little Rock, AR and Koc University School of Medicine, Istanbul, Turkey (M.C.); University of Texas Health Science Center, Houston (K.C.); University of Arkansas for Medical Sciences, Little Rock (A.H.); Athens Medical School, Hippokration General Hospital, Greece (K.T.); University of Alabama at Birmingham (M.A.L.); Detroit Medical Center, Cardiovascular Institute, MI (C.L.G.); and Citizens Memorial Hospital, Bolivar, MO and University of Missouri, Columbia (K.M.). herrmann.joerg@mayo.edu.
authors.forename: Joerg
authors.initials: J
authors.lastname: Herrmann
authors.affiliation: From Mayo Clinic, Division of Cardiovascular Diseases, Rochester, MN (J.H.); University of California at Los Angeles, Division of Cardiology, Los Angeles (E.-H.Y.); University of Texas, MD Anderson Cancer Center, Houston (C.A.I.); Arkansas Heart Hospital, Little Rock, AR and Koc University School of Medicine, Istanbul, Turkey (M.C.); University of Texas Health Science Center, Houston (K.C.); University of Arkansas for Medical Sciences, Little Rock (A.H.); Athens Medical School, Hippokration General Hospital, Greece (K.T.); University of Alabama at Birmingham (M.A.L.); Detroit Medical Center, Cardiovascular Institute, MI (C.L.G.); and Citizens Memorial Hospital, Bolivar, MO and University of Missouri, Columbia (K.M.).
authors.forename: Eric H
authors.initials: EH
authors.lastname: Yang
authors.affiliation: From Mayo Clinic, Division of Cardiovascular Diseases, Rochester, MN (J.H.); University of California at Los Angeles, Division of Cardiology, Los Angeles (E.-H.Y.); University of Texas, MD Anderson Cancer Center, Houston (C.A.I.); Arkansas Heart Hospital, Little Rock, AR and Koc University School of Medicine, Istanbul, Turkey (M.C.); University of Texas Health Science Center, Houston (K.C.); University of Arkansas for Medical Sciences, Little Rock (A.H.); Athens Medical School, Hippokration General Hospital, Greece (K.T.); University of Alabama at Birmingham (M.A.L.); Detroit Medical Center, Cardiovascular Institute, MI (C.L.G.); and Citizens Memorial Hospital, Bolivar, MO and University of Missouri, Columbia (K.M.).
authors.forename: Cezar A
authors.initials: CA
authors.lastname: Iliescu
authors.affiliation: From Mayo Clinic, Division of Cardiovascular Diseases, Rochester, MN (J.H.); University of California at Los Angeles, Division of Cardiology, Los Angeles (E.-H.Y.); University of Texas, MD Anderson Cancer Center, Houston (C.A.I.); Arkansas Heart Hospital, Little Rock, AR and Koc University School of Medicine, Istanbul, Turkey (M.C.); University of Texas Health Science Center, Houston (K.C.); University of Arkansas for Medical Sciences, Little Rock (A.H.); Athens Medical School, Hippokration General Hospital, Greece (K.T.); University of Alabama at Birmingham (M.A.L.); Detroit Medical Center, Cardiovascular Institute, MI (C.L.G.); and Citizens Memorial Hospital, Bolivar, MO and University of Missouri, Columbia (K.M.).
authors.forename: Mehmet
authors.initials: M
authors.lastname: Cilingiroglu
authors.affiliation: From Mayo Clinic, Division of Cardiovascular Diseases, Rochester, MN (J.H.); University of California at Los Angeles, Division of Cardiology, Los Angeles (E.-H.Y.); University of Texas, MD Anderson Cancer Center, Houston (C.A.I.); Arkansas Heart Hospital, Little Rock, AR and Koc University School of Medicine, Istanbul, Turkey (M.C.); University of Texas Health Science Center, Houston (K.C.); University of Arkansas for Medical Sciences, Little Rock (A.H.); Athens Medical School, Hippokration General Hospital, Greece (K.T.); University of Alabama at Birmingham (M.A.L.); Detroit Medical Center, Cardiovascular Institute, MI (C.L.G.); and Citizens Memorial Hospital, Bolivar, MO and University of Missouri, Columbia (K.M.).
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Charitakis
authors.affiliation: From Mayo Clinic, Division of Cardiovascular Diseases, Rochester, MN (J.H.); University of California at Los Angeles, Division of Cardiology, Los Angeles (E.-H.Y.); University of Texas, MD Anderson Cancer Center, Houston (C.A.I.); Arkansas Heart Hospital, Little Rock, AR and Koc University School of Medicine, Istanbul, Turkey (M.C.); University of Texas Health Science Center, Houston (K.C.); University of Arkansas for Medical Sciences, Little Rock (A.H.); Athens Medical School, Hippokration General Hospital, Greece (K.T.); University of Alabama at Birmingham (M.A.L.); Detroit Medical Center, Cardiovascular Institute, MI (C.L.G.); and Citizens Memorial Hospital, Bolivar, MO and University of Missouri, Columbia (K.M.).
authors.forename: Abdul
authors.initials: A
authors.lastname: Hakeem
authors.affiliation: From Mayo Clinic, Division of Cardiovascular Diseases, Rochester, MN (J.H.); University of California at Los Angeles, Division of Cardiology, Los Angeles (E.-H.Y.); University of Texas, MD Anderson Cancer Center, Houston (C.A.I.); Arkansas Heart Hospital, Little Rock, AR and Koc University School of Medicine, Istanbul, Turkey (M.C.); University of Texas Health Science Center, Houston (K.C.); University of Arkansas for Medical Sciences, Little Rock (A.H.); Athens Medical School, Hippokration General Hospital, Greece (K.T.); University of Alabama at Birmingham (M.A.L.); Detroit Medical Center, Cardiovascular Institute, MI (C.L.G.); and Citizens Memorial Hospital, Bolivar, MO and University of Missouri, Columbia (K.M.).
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Toutouzas
authors.affiliation: From Mayo Clinic, Division of Cardiovascular Diseases, Rochester, MN (J.H.); University of California at Los Angeles, Division of Cardiology, Los Angeles (E.-H.Y.); University of Texas, MD Anderson Cancer Center, Houston (C.A.I.); Arkansas Heart Hospital, Little Rock, AR and Koc University School of Medicine, Istanbul, Turkey (M.C.); University of Texas Health Science Center, Houston (K.C.); University of Arkansas for Medical Sciences, Little Rock (A.H.); Athens Medical School, Hippokration General Hospital, Greece (K.T.); University of Alabama at Birmingham (M.A.L.); Detroit Medical Center, Cardiovascular Institute, MI (C.L.G.); and Citizens Memorial Hospital, Bolivar, MO and University of Missouri, Columbia (K.M.).
authors.forename: Massoud A
authors.initials: MA
authors.lastname: Leesar
authors.affiliation: From Mayo Clinic, Division of Cardiovascular Diseases, Rochester, MN (J.H.); University of California at Los Angeles, Division of Cardiology, Los Angeles (E.-H.Y.); University of Texas, MD Anderson Cancer Center, Houston (C.A.I.); Arkansas Heart Hospital, Little Rock, AR and Koc University School of Medicine, Istanbul, Turkey (M.C.); University of Texas Health Science Center, Houston (K.C.); University of Arkansas for Medical Sciences, Little Rock (A.H.); Athens Medical School, Hippokration General Hospital, Greece (K.T.); University of Alabama at Birmingham (M.A.L.); Detroit Medical Center, Cardiovascular Institute, MI (C.L.G.); and Citizens Memorial Hospital, Bolivar, MO and University of Missouri, Columbia (K.M.).
authors.forename: Cindy L
authors.initials: CL
authors.lastname: Grines
authors.affiliation: From Mayo Clinic, Division of Cardiovascular Diseases, Rochester, MN (J.H.); University of California at Los Angeles, Division of Cardiology, Los Angeles (E.-H.Y.); University of Texas, MD Anderson Cancer Center, Houston (C.A.I.); Arkansas Heart Hospital, Little Rock, AR and Koc University School of Medicine, Istanbul, Turkey (M.C.); University of Texas Health Science Center, Houston (K.C.); University of Arkansas for Medical Sciences, Little Rock (A.H.); Athens Medical School, Hippokration General Hospital, Greece (K.T.); University of Alabama at Birmingham (M.A.L.); Detroit Medical Center, Cardiovascular Institute, MI (C.L.G.); and Citizens Memorial Hospital, Bolivar, MO and University of Missouri, Columbia (K.M.).
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Marmagkiolis
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects*; D054715:Cardiotoxins / Q000009:adverse effects*; D002318:Cardiovascular Diseases / Q000139:chemically induced* / Q000175:diagnosis; D006801:Humans; D009369:Neoplasms / Q000175:diagnosis / Q000188:drug therapy*
chemical_list: D000970:Antineoplastic Agents; D054715:Cardiotoxins
keywords: angina pectoris; chemotherapy; complications, cardiovascular; coronary vasospasm; drug therapy; endothelial cells