Mitochondrial intoxication by anthracyclines

Anthracyclines (ANTs), thanks to their broad spectrum of therapeutic efficacy, represent a mainstay in the treatment of both hematological and solid tumors. However, in spite of their extensive clinical use, the major drawback of these highly potent drugs is toxicity to nontargeted tissues, which can require treatment discontinuation or the usage of lower and less effective doses of chemotherapy, with a negative impact on cancer patient prognosis and well-being. Most studies show that cardiotoxicity represents the most severe side effect of ANTs. However, in the past years, there is a growing recognition of the detrimental effects of these drugs on other organs such as the brain, skeletal muscle, kidney, and liver among others. Common to all these targets, there is evidence that ANTs mediate their toxicity through the ability to accumulate within mitochondria and impair their function at multiple levels. The harmful effects given by ANTs are indeed because of the fact that these targeted organelles are crucial not only for ATP production but also for calcium homeostasis, redox regulation, and apoptosis. In this chapter, we will mainly focus on the molecular mechanisms whereby ANTs intoxicate mitochondria in different organs with a brief excursus on the clinical manifestations on cancer patients due to the poisonous effects of these antineoplastic compounds.