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

Ghigo A. Ameri P. Asnani A. Bertero E. de Boer R.A. Farmakis D. González A. Heymans S. Ibáñez B. López-Fernández T. Lyon A.R. Pollesello P. Rakisheva A. Stellos K. Streckfuss-Bömeke K. Tocchetti C.G. Thum T. van der Meer P. Van Rooij E. Ponikowski P. Metra M. Rosano G. Van Linthout S.
June 2025 John Wiley and Sons Ltd

European Journal of Heart Failure
2025 #27 Issue 6 1028 - 1046 pp.

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.

Anticancer therapy , Cancer , Cardiotoxicity , Immunotherapy , Preclinical models

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Molecular Biotechnology Center Guido Tarone, Department of Molecular Biotechnology and Health Sciences, University of Torino, Turin, Italy
Cardiac, Vascular, and Thoracic Department, IRCCS Ospedale Policlinico San Martino, Genoa, Italy
Department of Internal Medicine, University of Genova, Genoa, Italy
Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, United States
Cardiovascular Institute, Thorax Center, Department of Cardiology, Erasmus Medical Center, Rotterdam, Netherlands
Department of Cardiology, Athens University Hospital Attikon, National and Kapodistrian University of Athens Medical School, Athens, Greece
Program of Cardiovascular Diseases, Foundation for Applied Medical Research (CIMA), Department of Cardiology, Clínica Universidad de Navarra, Instituto de Investigación Sanitaria de Navarra (IdiSNA), Universidad de Navarra, Pamplona, Spain
Centro de Investigación Biomédica en Red Cardiovascular (CIBERCV), Instituto de Salud Carlos III, Madrid, Spain
Department of Cardiology, CARIM Cardiovascular Research Institute Maastricht, Maastricht University Medical Centre, Maastricht, Netherlands
Centre of Cardiovascular Research, University of Leuven, Leuven, Belgium
Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain
Cardiology Department, IIS-Fundación Jiménez Díaz Hospital, Madrid, Spain
Cardiology Department, La Paz University Hospital, Madrid, Spain
IdiPAZ research Institute, Madrid, Spain
Cardiology Department, Quironsalud Madrid University Hospital, Madrid, Spain
Cardio-Oncology Centre of Excellence, Royal Brompton Hospital, London, United Kingdom
Content and Communication, Branded Products, Orion Pharma, Espoo, Finland
Department of Cardiology, City Cardiology Center, Almaty, Kazakhstan
Department of Cardiology, Qonaev City Hospital, Almaty, Kazakhstan
Department of Cardiovascular Research, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
German Centre for Cardiovascular Research (DZHK), Partner Site Heidelberg/Mannheim, Mannheim, Germany
Biosciences Institute, Vascular Biology and Medicine Theme, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom
Medizinische Klinik I, Department of Cardiology, Angiology, Haemostaseology and Intensive Care Medicine, University Hospital Mannheim of the Heidelberg University, Mannheim, Germany
Clinic for Cardiology and Pneumology, Georg-August University Göttingen, Göttingen, Germany
Medical Clinic I, Cardiology and Angiology, Justus-Liebig-University, Giessen, Germany
Institute of Pharmacology and Toxicology, University of Würzburg, Würzburg, Germany
Comprehensive Heart Failure Center Würzburg, Würzburg, Germany
Department of Translational Medical Sciences (DISMET), Center for Basic and Clinical Immunology Research (CISI), Interdepartmental Center of Clinical and Translational Sciences (CIRCET), Interdepartmental Hypertension Research Center (CIRIAPA), Federico II University, Naples, Italy
Institute of Molecular and Translational Therapeutic Strategies (IMTTS), Hannover Medical School, Hannover, Germany
Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and University Medical Center Utrecht, Utrecht, Netherlands
Department of Cardiology, University Medical Center Utrecht, Utrecht, Netherlands
Center for Heart Diseases, University Hospital, Wroclaw Medical University, Wroclaw, Poland
Institute of Cardiology, ASST Spedali Civili, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, Brescia, Italy
Department of Human Sciences and Promotion of Quality of Life, San Raffaele Open University of Rome, Rome, Italy
Cardiology, San Raffaele Cassino Hospital, Cassino, Italy
Berlin Institute of Health at Charité-Universitätsmedizin Berlin, BIH Center for Regenerative Therapies (BCRT), Berlin, Germany
German Center for Cardiovascular Research (DZHK), Partner site Berlin, Berlin, Germany

Molecular Biotechnology Center Guido Tarone
Cardiac
Department of Internal Medicine
Division of Cardiovascular Medicine
Cardiovascular Institute
Department of Cardiology
Program of Cardiovascular Diseases
Centro de Investigación Biomédica en Red Cardiovascular (CIBERCV)
Department of Cardiology
Centre of Cardiovascular Research
Centro Nacional de Investigaciones Cardiovasculares
Cardiology Department
Cardiology Department
IdiPAZ research Institute
Cardiology Department
Cardio-Oncology Centre of Excellence
Content and Communication
Department of Cardiology
Department of Cardiology
Department of Cardiovascular Research
German Centre for Cardiovascular Research (DZHK)
Biosciences Institute
Medizinische Klinik I
Clinic for Cardiology and Pneumology
Medical Clinic I
Institute of Pharmacology and Toxicology
Comprehensive Heart Failure Center Würzburg
Department of Translational Medical Sciences (DISMET)
Institute of Molecular and Translational Therapeutic Strategies (IMTTS)
Department of Cardiology
Hubrecht Institute
Department of Cardiology
Center for Heart Diseases
Institute of Cardiology
Department of Human Sciences and Promotion of Quality of Life
Cardiology
Berlin Institute of Health at Charité-Universitätsmedizin Berlin
German Center for Cardiovascular Research (DZHK)

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