Cardiotoxic effects of angiogenesis inhibitors

Dobbin, S. J.H. , Petrie, M. C. , Myles, R. C. , Touyz, R. M. and Lang, N. N. (2021) Cardiotoxic effects of angiogenesis inhibitors. Clinical Science, 135(1), pp. 71-100. (doi: 10.1042/CS20200305) (PMID:33404052) (PMCID:PMC7812690)

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The development of new therapies for cancer has led to dramatic improvements in survivorship. Angiogenesis inhibitors represent one such advancement, revolutionising treatment for a wide range of malignancies. However, these drugs are associated with cardiovascular toxicities which can impact optimal cancer treatment in the short-term and may lead to increased morbidity and mortality in the longer term. Vascular endothelial growth factor inhibitors (VEGFIs) are associated with hypertension, left ventricular systolic dysfunction (LVSD) and heart failure as well as arterial and venous thromboembolism, QTc interval prolongation and arrhythmia. The mechanisms behind the development of VEGFI-associated LVSD and heart failure likely involve the combination of a number of myocardial insults. These include direct myocardial effects, as well as secondary toxicity via coronary or peripheral vascular damage. Cardiac toxicity may result from the ‘on-target’ effects of VEGF inhibition or ‘off-target’ effects resulting from inhibition of other tyrosine kinases. Similar mechanisms may be involved in the development of VEGFI-associated right ventricular (RV) dysfunction. Some VEGFIs can be associated with QTc interval prolongation and an increased risk of ventricular and atrial arrhythmia. Further pre-clinical and clinical studies and trials are needed to better understand the impact of VEGFI on the cardiovascular system. Once mechanisms are elucidated, therapies can be investigated in clinical trials and surveillance strategies for identifying VEGFI-associated cardiovascular complications can be developed.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Myles, Dr Rachel and Petrie, Professor Mark and Dobbin, Dr Stephen and Touyz, Professor Rhian and Lang, Professor Ninian
Authors: Dobbin, S. J.H., Petrie, M. C., Myles, R. C., Touyz, R. M., and Lang, N. N.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
Journal Name:Clinical Science
Publisher:Portland Press
ISSN (Online):1470-8736
Published Online:06 January 2021
Copyright Holders:Copyright © 2021 The Authors
First Published:First published in Clinical Science 135(1): 71-100
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
306137MARKERS AND MEDIATORS OF ANGIOGENESIS INHIBITOR-INDUCED VASCULAR AND MYOCARDIAL TOXICITY: A Prospective Study in Patients with CancerNinian LangBritish Heart Foundation (BHF)PG/19/64/34434CAMS - Cardiovascular Science
303944BHF Centre of ExcellenceRhian TouyzBritish Heart Foundation (BHF)RE/18/6/34217CAMS - Cardiovascular Science
171105Heterogeneity of sympathetic stimulation as a mechanism of ventricular arrhythmia following myocardial infarctionRachel MylesWellcome Trust (WELLCOTR)105907/Z/14/ZInstitute of Cardiovascular & Medical Sciences
300689Vascular Noxs as therapeutic targets and biomarkers in hypertensionRhian TouyzBritish Heart Foundation (BHF)CH/12/4/29762CAMS - Cardiovascular Science