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Update on preclinical models of cancer therapy-related cardiac dysfunction: Challenges and perspectives. A scientific statement of the Heart Failure Association (HFA) of the ESC, the ESC Council of Cardio-Oncology, and the ESC Working Group on Cellular Biology of the Heart

Lookup NU author(s): Professor Konstantinos StellosORCiD

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).

Abstract

© 2025 The Author(s). European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology. New anticancer therapies with potential cardiovascular side effects are continuously being introduced into clinical practice, with new and often unexpected toxicities becoming apparent only after clinical introduction. These unknown toxicities should be identified and understood beforehand to better prepare patients and physicians, enabling the implementation of effective treatments. Therefore, there is a crucial need for appropriate preclinical models to understand the biological basis of their cardiotoxicity. This scientific statement summarizes the preclinical models hitherto used, from in vitro two- and three-dimensional human systems to small and large animals, to pinpoint the molecular mechanisms behind the cardiotoxicity of new-generation anticancer therapies, particularly immunotherapies, and to develop potential cardioprotective strategies. Furthermore, it discusses how preclinical models have contributed to the provocative concept of heart failure being potentially tumorigenic and how the discovery of drugs with both anticancer and cardioprotective actions has revealed a common mechanistic basis for heart failure and cancer. Finally, it discusses the existing gaps between preclinical models and clinical observations in patients, how these discrepancies affect regulatory pathways and the drug development process in cardio-oncology and provides recommendations for closing these gaps.

Publication metadata

Author(s): Ghigo A, Ameri P, Asnani A, Bertero E, de Boer RA, Farmakis D, Gonzalez A, Heymans S, Ibanez B, Lopez-Fernandez T, Lyon AR, Pollesello P, Rakisheva A, Stellos K, Streckfuss-Bomeke K, Tocchetti CG, Thum T, van der Meer P, Van Rooij E, Ponikowski P, Metra M, Rosano G, Van Linthout S

Publication type: Article

Publication status: Published

Journal: European Journal of Heart Failure

Year: 2025

Volume: 27

Issue: 6

Pages: 1028-1046

Print publication date: 01/06/2025

Online publication date: 11/03/2025

Acceptance date: 14/02/2025

Date deposited: 10/04/2025

ISSN (print): 1388-9842

ISSN (electronic): 1879-0844

Publisher: John Wiley and Sons Ltd

URL: https://doi.org/10.1002/ejhf.3636

DOI: 10.1002/ejhf.3636

PubMed id: 40069106

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