Cancer therapy-related cardiovascular toxicity testing: an overview of experimental preclinical in vitro models and how to best use them in combination with animal models, omics and AI-based in silico approaches

Abstract Cancer therapy-related cardiovascular toxicity (CTR-CVT) remains a major contributor to morbidity and mortality among cancer survivors. While advances in cancer therapy have significantly improved survival rates, many of these treatments come at the cost of unintended cardiovascular damage. This creates a complex and pressing challenge in cardio-oncology: how to treat cancer, while minimising harm to the heart effectively. A central goal in cardio-oncology is therefore not only to understand the mechanisms of therapy-induced cardiac injury, but also to develop reliable, and predictive approaches to detect and assess CTR-CVT as early as possible, ideally before irreversible damage occurs. This review aims to explore the major preclinical in vitro models used to understand and predict cardiotoxicities induced by anti-cancer treatments, from traditional cell culture to the most recent technologies, such as 3D-bioprinting, organoids, organs-on-a-chip and artificial intelligence-based in silico approaches. Advantages and limitations are addressed for each experimental model to help guide future studies in cardiooncology that might better translate findings from the bench to the bedside.