Journal
JACC: CARDIOONCOLOGY
Volume 4, Issue 1, Pages 1-18Publisher
ELSEVIER
DOI: 10.1016/j.jaccao.2022.01.096
Keywords
BRAF inhibitor; cardio; oncology; cardiovascular toxicity; hypertension; left ventricular systolic; dysfunction; MEK inhibitor; melanoma
Categories
Funding
- Roche Diagnostics, Switzerland
- British Heart Foundation Centre of Research Excellence Grant [RE/18/6/34217]
- Adaptimmune
- Astellas
- Bayer
- Boehringer Ingelheim
- Celgene
- Codiak
- Esai
- GlaxoSmithKline
- iOncture
- Johnson and Johnson
- Merck Sharp Dohme
- Novartis Pfizer
- Roche/Genentech
- Roche
- SQ Innovations
- AstraZeneca
- Novartis
- Novo Nordisk
- Medtronic
- Boston Scientific
- Pharmacosmos
- 3R LifeSciences
Ask authors/readers for more resources
BRAF and MEK inhibitors have revolutionized melanoma treatment by targeting the signaling pathway involved in cell proliferation. However, they are also associated with adverse cardiovascular effects such as hypertension and cardiac dysfunction. It is important to conduct baseline cardiovascular assessment and follow-up to optimize cancer treatment while minimizing cardiovascular side effects.
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. (J Am Coll Cardiol CardioOnc 2022;4:1-18) (c) 2022 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
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