Exploring Anthracycline-Induced Cardiotoxicity from the Perspective of Protein Quality Control.

ABSTRACT

Anthracyclines are effective anticancer drugs; however, their use is restricted because of their dose-dependent, time-dependent and irreversible myocardial toxicity. The mechanism of anthracycline cardiotoxicity has been widely studied but remains unclear. Protein quality control is crucial to the stability of the intracellular environment and, ultimately, to the heart because cardiomyocytes are terminally differentiated. Two evolutionarily conserved mechanisms, autophagy, and the ubiquitin-proteasome system, synergistically degrade misfolded proteins and remove defective organelles. Recent studies demonstrated the importance of these mechanisms. Further studies will reveal the detailed metabolic pathway and metabolic control of the protein quality control mechanism integrated into anthracycline-induced cardiotoxicity. This review provides theoretical support for clinicians in the application and management of anthracyclines.