Proteomics of RARG-variant S427l cardioids exposed to doxorubicin and their role in doxorubicin-induced cardiotoxicity

Doxorubicin is an effective anthracycline anticancer drug that is commonly used as a chemotherapeutic agent against various malignancies. However, doxorubicin's use is limited by one major adverse effect associated with it, cardiotoxicity. Studies have shown that a genetic mutation in the retinoic acid receptor gamma in the S427L position increases susceptibility to cardiotoxicity. However, the mechanism of action that causes doxorubicin-induced cardiotoxicity is not yet known but is thought to be associated with autophagy. Using 3D cardiac tissue structures known as cardioids, they will be dosed over four weeks at a concentration of 100 µg/L of doxorubicin. The proteomic profiles of these cardioids are analysed using mass spectrometry. The results showed that major pathways in ferroptosis, autophagy, and mitophagy were significantly affected, suggesting possible mechanisms of action that cause doxorubicin-induced cardiotoxicity.