Cardiovascular toxicity of angiogenesis inhibitors and immune checkpoint inhibitors: synergistic anti-tumour effects at the cost of increased cardiovascular risk?

Autor:	van Dorst DCH; Division of Vascular Medicine and Pharmacology, Department of Internal Medicine, Erasmus MC University Medical Center, Rotterdam, The Netherlands.; Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands., van Doorn L; Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands., Mirabito Colafella KM; Cardiovascular Disease Program, Biomedicine Discovery Institute and Department of Physiology, Monash University, Melbourne, Australia., Manintveld OC; Department of Cardiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands., Hassing HC; Department of Cardiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands., Danser AHJ; Division of Vascular Medicine and Pharmacology, Department of Internal Medicine, Erasmus MC University Medical Center, Rotterdam, The Netherlands., Mathijssen RHJ; Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands., Versmissen J; Division of Vascular Medicine and Pharmacology, Department of Internal Medicine, Erasmus MC University Medical Center, Rotterdam, The Netherlands.; Department of Hospital Pharmacy, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
Jazyk:	angličtina
Zdroj:	Clinical science (London, England : 1979) [Clin Sci (Lond)] 2021 Jul 30; Vol. 135 (14), pp. 1649-1668.
DOI:	10.1042/CS20200300
Abstrakt:	In the past two decades, treatment outcomes for a wide range of malignancies have improved remarkably due to the development of novel anti-cancer therapies, including vascular endothelial growth factor inhibitors (VEGFIs) and immune checkpoint inhibitors (ICIs). Despite their unprecedented anti-tumour effects, it is becoming increasingly clear that both types of agents are associated with specific cardiovascular toxicity, including hypertension, congestive heart failure, myocarditis and acceleration of atherosclerosis. Currently, VEGFI and ICI combination therapy is recommended for the treatment of advanced renal cell carcinoma (RCC) and has shown promising treatment efficacy in other tumour types as well. Consequently, VEGFI and ICI combination therapy will most likely become an important therapeutic strategy for various malignancies. However, this combinatory approach is expected to be accompanied by a substantial increase in cardiovascular risk, as both types of agents could act synergistically to induce cardiovascular sequelae. Therefore, a comprehensive baseline assessment and adequate monitoring by specialised cardio-oncology teams is essential in case these agents are used in combination, particularly in high-risk patients. This review summarises the mechanisms of action and treatment indications for currently registered VEGFIs and ICIs, and discusses their main vascular and cardiac toxicity. Subsequently, we provide the biological rationales for the observed promising synergistic anti-tumour effects of combined VEGFI/ICI administration. Lastly, we speculate on the increased risk for cardiovascular toxicity in case these agents are used in combination and its implications and future directions for the clinical situation. (© 2021 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.)
Databáze:	MEDLINE
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