Novel molecular mechanisms of doxorubicin cardiotoxicity: latest leading-edge advances and clinical implications

Abstract

Doxorubicin (Dox) is among the most widely used cancer chemotherapeutic drugs. The clinical use of Dox is, however, limited due to its cardiotoxicity. Studies over the past several decades have suggested various mechanisms of Dox-induced cardiotoxicity (DIC). Among them are oxidative stress, topoisomerase inhibition, and mitochondrial damage. Several novel molecular targets and signaling pathways underlying DIC have emerged over the past few years. The most notable advances include discovery of ferroptosis as a major form of cell death in Dox cytotoxicity, and elucidation of the involvement of cardiogenetics and regulatory RNAs as well as multiple other targets in DIC. In this review, we discuss these advances, focusing on latest cutting-edge research discoveries from mechanistic studies reported in influential journals rather than surveying all research studies available in the literature.

Keywords: Cardiogenetics; Cardiomyopathy; Cardiotoxicity; Doxorubicin; Ferroptosis; Heme; Hemopexin; Macrophage; Mitochondria; Nrf1; Regulatory RNA.