Chemo-/radiotherapy-induced cardiomyopathy: roles of mitochondria and endoplasmic reticulum

Chemo-/radiotherapy-induced cardiomyopathy is a clinical challenge for patients with cancer, characterized by detrimental effects on cardiac structure and function. To date, numerous experimental and clinical investigations have revealed that numerous mechanisms, such as oxidative damage, contribute to chemo-/radiotherapy-induced cardiomyopathy. Chronic oxidative stress and reactive oxygen species (ROS) production following damage to mitochondria and the endoplasmic reticulum (ER) play a fundamental role in the progression of cell death, inflammation, and fibrosis, leading to heart failure and unusual changes in the heart structure. This review delves into the mechanisms of cardiotoxicity induced by chemotherapy and radiotherapy, highlighting the pivotal role of mitochondrial dysfunction and subsequent oxidative stress and cell death. The interplay between mitochondrial and ER dysfunction can also be offered as a paramount factor in the development of cardiomyopathy. We review how damage to these organelles may trigger cardiac injury through crosstalk with other mechanisms such as activation of pro-oxidant enzymes, inflammation, fibrosis, and other important processes.