Cellular Mechanisms Underlying Cardiotoxicities of Cancer Therapies

Dilated cardiomyopathy (DCM) is the most prevalent heart muscle disease, with a 50% survival rate within five years of diagnosis. In the progression of DCM, heart muscle cells, known as cardiomyocytes, elongate and weaken the ventricular walls of the heart. A number of DCM cases have been linked with cancer therapy treatment, with several studies observing the effect of these treatments on animal cardiomyocytes. We examined the impact of cancer therapies on human cardiomyocytes in vitro in order to glean an understanding of how the toxicity is expressed in humans. We treated human induced pluripotent stem cell cardiomyocytes (hiCM) with various inhibitory drugs, and, through phase-contrast and immunofluorescence microscopy, hiCM were quantified over time, revealing a strong correlation between high drug concentration and cell death. Our data suggests that cardiomyocytes may be dying from a necrotic death, due to the observed health and functionality of the cardiomyocytes until the moment of destruction.