Abstract
Although survival of patients with different types of cancer has improved, cardiotoxicity induced by anti-neoplastic drugs remains a critical issue. Cardiac dysfunction after treatment with anthracyclines has historically been a major problem. However, also targeted therapies and biological molecules can induce reversible and irreversible cardiac dysfunction. Over the last years, cancer immunotherapies haverevolutionized the clinical management of a wide spectrum of solid and hematopoietic malignancies previously endowed with poor prognosis. Immune checkpoint inhibitors are at the forefront of immunotherapy: the two most prominent are the targeting of cytotoxic-T-lymphocyte-associated antigen 4 (CTLA- 4) and of programmed cell death 1 (PD-1) and its ligand PD-L1. Ipilimumab (anti-CTLA-4) is the godfather of checkpoint inhibitors, whereas several blocking monoclonal antibodies targeting PD-1 (nivolumab and pembrolizumab) and PD-L1 (atezolizumab, durvalumab, avelumab, and BMS-946559) have been developed. Inhibitors of CTLA-4 and PD-1/PD-L1 pathway can unleash anti-tumor immunity and mediate cancer regressions. Although CTLA-4 inhibitors and PD-1 and PD-L1 blocking agents are frequently associated with a wide spectrum of immune-related adverse events, cardiac toxicity has been underestimated. However, early animal studies have demonstrated that after CTLA-4 inhibition and PD-1 deletion autoimmune myocarditis can occur. Moreover, PD-1 and PD-L1 can be expressed in rodent and human cardiomyocytes. During the last years several cases of fatal heart failure have been documented in melanoma patients treated with checkpoint inhibitors. The recent experience with cardiovascular toxic effects associated with checkpoint inhibitors introduces important concepts biologically and clinically relevant for future oncology trials and clinical practice.
Keywords: Cancer, cardiac toxicity, checkpoints, CTLA-4, melanoma, myocarditis, PD-1, PD-L1.
Current Medicinal Chemistry
Title:Immune Checkpoint Inhibitors and Cardiac Toxicity: An Emerging Issue
Volume: 25 Issue: 11
Author(s): Gilda Varricchi*, Giancarlo Marone, Valentina Mercurio, Maria Rosaria Galdiero, Domenico Bonaduce and Carlo G. Tocchetti*
Affiliation:
- Department of Translational Medical Sciences – Federico II University, Naples,Italy
- Department of Translational Medical Sciences – Federico II University, Naples,Italy
Keywords: Cancer, cardiac toxicity, checkpoints, CTLA-4, melanoma, myocarditis, PD-1, PD-L1.
Abstract: Although survival of patients with different types of cancer has improved, cardiotoxicity induced by anti-neoplastic drugs remains a critical issue. Cardiac dysfunction after treatment with anthracyclines has historically been a major problem. However, also targeted therapies and biological molecules can induce reversible and irreversible cardiac dysfunction. Over the last years, cancer immunotherapies haverevolutionized the clinical management of a wide spectrum of solid and hematopoietic malignancies previously endowed with poor prognosis. Immune checkpoint inhibitors are at the forefront of immunotherapy: the two most prominent are the targeting of cytotoxic-T-lymphocyte-associated antigen 4 (CTLA- 4) and of programmed cell death 1 (PD-1) and its ligand PD-L1. Ipilimumab (anti-CTLA-4) is the godfather of checkpoint inhibitors, whereas several blocking monoclonal antibodies targeting PD-1 (nivolumab and pembrolizumab) and PD-L1 (atezolizumab, durvalumab, avelumab, and BMS-946559) have been developed. Inhibitors of CTLA-4 and PD-1/PD-L1 pathway can unleash anti-tumor immunity and mediate cancer regressions. Although CTLA-4 inhibitors and PD-1 and PD-L1 blocking agents are frequently associated with a wide spectrum of immune-related adverse events, cardiac toxicity has been underestimated. However, early animal studies have demonstrated that after CTLA-4 inhibition and PD-1 deletion autoimmune myocarditis can occur. Moreover, PD-1 and PD-L1 can be expressed in rodent and human cardiomyocytes. During the last years several cases of fatal heart failure have been documented in melanoma patients treated with checkpoint inhibitors. The recent experience with cardiovascular toxic effects associated with checkpoint inhibitors introduces important concepts biologically and clinically relevant for future oncology trials and clinical practice.
Export Options
About this article
Cite this article as:
Varricchi Gilda *, Marone Giancarlo , Mercurio Valentina, Galdiero Rosaria Maria , Bonaduce Domenico and Tocchetti G. Carlo*, Immune Checkpoint Inhibitors and Cardiac Toxicity: An Emerging Issue, Current Medicinal Chemistry 2018; 25 (11) . https://dx.doi.org/10.2174/0929867324666170407125017
DOI https://dx.doi.org/10.2174/0929867324666170407125017 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Applications of Stem Cell Therapy for Physeal Injuries.
Current Stem Cell Research & Therapy Antithrombotic Options for Atrial Fibrillation in 2012
Cardiovascular & Hematological Disorders-Drug Targets Recent Progress on Antifungal Drug Development
Current Pharmaceutical Biotechnology Signaling Epicenters: The Role of Caveolae and Caveolins in Volatile Anesthetic Induced Cardiac Protection
Current Pharmaceutical Design Contrast Echocardiography: An Update on Clinical Applications
Current Pharmaceutical Design A Scientometrics Analysis and Visualization of Depressive Disorder
Current Neuropharmacology Molecular Mechanism of Anti-tumor Effect by Triptolide in Hematological Malignancies
Current Signal Transduction Therapy Biological Roles of the Eclectic Chromogranin-A-derived Peptide Catestatin
Current Medicinal Chemistry Design and Synthesis of Thiazolidinedione Derivates as Selective PPARγ Modulators
Letters in Drug Design & Discovery Meet Our Editor:
Current Hypertension Reviews Surgical Ventricular Restoration: An Operation To Reverse Remodeling - The Basic Science (Part I)
Current Cardiology Reviews Renal Innervation in Resistant Hypertension: A Review of Pathophysiology and Renal Denervation as Potential Treatment
Current Hypertension Reviews MicroRNA Regulation in Cardiovascular Disease
Current Drug Targets Beta-Adrenoreceptor Modulation of Metabolic, Endocrine and Immunologic Function During Critical Illness
Endocrine, Metabolic & Immune Disorders - Drug Targets FK506-Binding Proteins and Their Diverse Functions
Current Molecular Pharmacology Prevention and Treatment of Regimen-Related Mucosal Toxicity
Recent Patents on Anti-Cancer Drug Discovery Drugs Affecting Blood Pressure Variability: An Update
Current Pharmaceutical Design Cardioprotective Effects of Natural Products <i>via</i> the Nrf2 Signaling Pathway
Current Vascular Pharmacology Platelet-Monocyte Interactions - A Dangerous Liaison Linking Thrombosis, Inflammation and Atherosclerosis
Current Medicinal Chemistry Immunomodulation Mechanism of Antidepressants: Interactions between Serotonin/Norepinephrine Balance and Th1/Th2 Balance
Current Neuropharmacology