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RESEARCH PRODUCT
Antineoplastic Drug-Induced Cardiotoxicity: A Redox Perspective
Gilda VarricchiGilda VarricchiPietro AmeriChristian CadedduAlessandra GhigoRosalinda MadonnaRosalinda MadonnaGiancarlo MaroneGiancarlo MaroneValentina MercurioInes MonteGiuseppina NovoPaolo ParrellaFlora PirozziAntonio PecoraroPaolo SpallarossaConcetta ZitoGiuseppe MercuroPasquale PagliaroCarlo G. Tocchettisubject
Stromal cellPhysiologymedicine.medical_treatmentTyrosine kinase inhibitorChemotherapy; HER-2 inhibitors; Oxidative/nitrosative stress; Tyrosine kinase inhibitors; Vascular endothelial growth factorReviewOxidative phosphorylation030204 cardiovascular system & hematologyMitochondrionPharmacologyChemotherapy; HER-2 inhibitors; Oxidative/nitrosative stress; Tyrosine kinase inhibitors; Vascular endothelial growth factor; Physiology; Physiology (medical)chemotherapyHER-2 inhibitorlcsh:Physiology03 medical and health scienceschemistry.chemical_compound0302 clinical medicinePhysiology (medical)tyrosine kinase inhibitorsMedicinechemotherapy HER-2 inhibitors oxidative/nitrosative stress vascular endothelial growth factor tyrosine kinase inhibitorsReactive nitrogen specieschemistry.chemical_classificationCardioprotectionReactive oxygen speciesChemotherapyCardiotoxicitylcsh:QP1-981vascular endothelial growth factorbusiness.industryOxidative/nitrosative strechemistry030220 oncology & carcinogenesisbusinessHER-2 inhibitorsoxidative/nitrosative stressdescription
Antineoplastic drugs can be associated with several side effects, including cardiovascular toxicity (CTX). Biochemical studies have identified multiple mechanisms of CTX. Chemoterapeutic agents can alter redox homeostasis by increasing the production of reactive oxygen species (ROS) and reactive nitrogen species RNS. Cellular sources of ROS/RNS are cardiomyocytes, endothelial cells, stromal and inflammatory cells in the heart. Mitochondria, peroxisomes and other subcellular components are central hubs that control redox homeostasis. Mitochondria are central targets for antineoplastic drug-induced CTX. Understanding the mechanisms of CTX is fundamental for effective cardioprotection, without compromising the efficacy of anticancer treatments. Type 1 CTX is associated with irreversible cardiac cell injury and is typically caused by anthracyclines and conventional chemotherapeutic agents. Type 2 CTX, associated with reversible myocardial dysfunction, is generally caused by biologicals and targeted drugs. Although oxidative/nitrosative reactions play a central role in CTX caused by different antineoplastic drugs, additional mechanisms involving directly and indirectly cardiomyocytes and inflammatory cells play a role in cardiovascular toxicities. Identification of cardiologic risk factors and an integrated approach using molecular, imaging, and clinical data may allow the selection of patients at risk of developing chemotherapy-related CTX. Although the last decade has witnessed intense research related to the molecular and biochemical mechanisms of CTX of antineoplastic drugs, experimental and clinical studies are urgently needed to balance safety and efficacy of novel cancer therapies. © 2018 Varricchi, Ameri, Cadeddu, Ghigo, Madonna, Marone, Mercurio, Monte, Novo, Parrella, Pirozzi, Pecoraro, Spallarossa, Zito, Mercuro, Pagliaro and Tocchetti.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2018-03-01 |