Mechanistic and clinical overview cardiovascular toxicity of BRAF and MEK inhibitors: JACC: CardioOncology state-of-the-art review

Glen, C., Tan, Y. Y., Waterston, A., Evans, T. R. J. , Jones, R. J. , Petrie, M. C. and Lang, N. N. (2022) Mechanistic and clinical overview cardiovascular toxicity of BRAF and MEK inhibitors: JACC: CardioOncology state-of-the-art review. JACC: CardioOncology, 4(1), pp. 1-18. (doi: 10.1016/j.jaccao.2022.01.096)

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Abstract

Rapidly accelerated fibrosarcoma B-type (BRAF) and mitogen-activated extracellular signal-regulated kinase (MEK) inhibitors have revolutionized melanoma treatment. Approximately half of patients with melanoma harbor a BRAF gene mutation with subsequent dysregulation of the RAF-MEK-ERK signaling pathway. Targeting this pathway with BRAF and MEK blockade results in control of cell proliferation and, in most cases, disease control. These pathways also have cardioprotective effects and are necessary for normal vascular and cardiac physiology. BRAF and MEK inhibitors are associated with adverse cardiovascular effects including hypertension, left ventricular dysfunction, venous thromboembolism, atrial arrhythmia, and electrocardiographic QT interval prolongation. These effects may be underestimated in clinical trials. Baseline cardiovascular assessment and follow-up, including serial imaging and blood pressure assessment, are essential to balance optimal anti-cancer therapy while minimizing cardiovascular side effects. In this review, an overview of BRAF/MEK inhibitor–induced cardiovascular toxicity, the mechanisms underlying these, and strategies for surveillance, prevention, and treatment of these effects are provided.

Item Type:Articles
Additional Information:NNL and CG are supported by an unrestricted grant from Roche Diagnostics, Switzerland. NNL and MCP are supported by a British Heart Foundation Centre of Research Excellence Grant (RE/18/6/34217).
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Lang, Dr Ninian and Evans, Professor Jeff and Tan, Dr Yun Yi and Petrie, Professor Mark and Jones, Professor Robert and Glen, Dr Claire
Authors: Glen, C., Tan, Y. Y., Waterston, A., Evans, T. R. J., Jones, R. J., Petrie, M. C., and Lang, N. N.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Journal Name:JACC: CardioOncology
Publisher:Elsevier
ISSN:2666-0873
ISSN (Online):2666-0873
Published Online:15 March 2022
Copyright Holders:Copyright © 2022 The Authors
First Published:First published in JACC: CardioOncology 4(1): 1-18
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
303944BHF Centre of ExcellenceColin BerryBritish Heart Foundation (BHF)RE/18/6/34217CAMS - Cardiovascular Science