Table 1.

Preclinical Models Available to Study Cancer Therapy-Associated Cardiovascular Toxicity

Model system	Strengths	Weaknesses	Examples
Cultured cell and organoid models
Rodent-derived CMs	Primary cells Neonatal cardiomyocytes: easily harvested with well-established protocols; easy to transfect	Neonatal cardiomyocytes: immature; express fetal gene program Adult cardiomyocytes: isolation and transfection are more challenging; contraction requires pacing; shorter time frame for performing assays	Anthracyclines2
Human cardiovascular cell lines (eg, hiPSC-CMs)	Can be expanded endlessly; derived from multiple easily accessible cell types; ability to study pathways specific to humans	Immature cells; experimental and genetic variability; optimal media conditions that replicate in vivo cardiotoxicity have not been clearly defined	Anthracyclines3 Trastuzumab4 Proteasome inhibitors5
Microtissues and organoid systems	More physiologically relevant than isolated cell culture; potential to study multiple cell types simultaneously	Need for manual cell injection, resulting in nonstandardized organoids; absence of in vivo cell-to-cell communication and environment	Sunitinib6
In vivo models
Zebratish	Vertebrate model with conservation of most disease-causing human genes; small size enables high-throughput screening; optical transparence facilitates imaging	Often used in embryonic/larval stage; 2-chamber heart without pulmonary circulation; zebrafish-specific reagents (eg, antibodies) may not be readily available	Anthracyclines7 Tyrosine kinase inhibitors8 Amyloid light-chain cardiotoxicity9
Rodents (mice, rats)	Most well-established in vivo model for studying toxicity; transgenic models and antibodies often already exist	Most models do not accurately reflect human comorbidities (hypertension, diabetes, aging) or concomitant cardiotoxic therapies	Anthracyclines10–12 HER2 inhibition1 Sunitinib13
Large animals (rabbits, swine, dogs)	Facilitate translation of diagnostic modalities and cardioprotective strategies	Costly and time-consuming; potential for gap in translation to humans	Anthracyclines14

HER2 indicates human epidermal growth factor receptor 2; HER2, human epidermal growth factor receptor 2; and hiPSC-CMs, human induced pluripotent stem cell-derived cardiomyocytes.