Modeling the Pharmacogenomics of Chemotherapy-Induced Cardiotoxicty Using hiPSC

It is well established that numerous chemotherapy drugs, whilst effective in treating a wide range of malignancies, can lead to cardiotoxicity that can lead to dysrythmias, cardiomyopathy, and heart failure.

At present, it is not possible to predict which patients will be affected by chemotherapy-induced cardiotoxicity (CIC). Here we demonstrate that patient-specific human induced pluripotent stem cell–derived cardiomyocytes (hiPSC-CMs) can recapitulate the predilection to CIC of individual patients at the cellular level. hiPSC-CMs derived from individuals with cancer who experienced CIC were consistently more sensitive to chemotherapy toxicity than hiPSC-CMs from patients who did not experience CIC. Our data indicate that hiPSC-CMs are a suitable platform to identify and characterize the genetic basis and molecular mechanisms of CIC.