LAUSR

The prognosis of patients with cancer has significantly improved in the past 20 years; thanks to optimization of chemotherapy protocols with established drugs, and the availability of molecules targeting new biological pathways. As cancer and cardiovascular diseases share many common biological processes, administration of anti-neoplastic drugs is often complicated with toxic cardiovascular side-effects. The primary aim of anti-cancer therapies is to prolong patient survival while maintaining a good quality of life. With prolonged survival and aging of patients treated for cancer, cardiotoxicities of anti-neoplastic molecules have become of concern. Initiation and maintenance of oncological treatments require careful evaluation of the risks of cardiotoxic side-effects without preventing patients from benefiting of the most effective anti-neoplastic treatments. Anthracyclines are used to treat a wide range of cancers including hematologic and breast malignancies and are one of the first anti-neoplastic drugs identified as cardiotoxic. In addition to the cardiotoxicity of anthracyclines, patients may also be exposed to newer agents that bear potential cardiac or vascular toxicities through different pathways. Anthracyclines are intercalating agents that inhibit rapidly proliferating cancer cells by stabilizing topoisomerase 2a complexes preventing DNA repair andRNA synthesis and leading to the death of tumor cells. However, anthracyclines also inhibit topoisomerase 2b, which is active in quiescent nonproliferating cells including cardiomyocytes, and may induce cellular apoptosis. In addition, anthracyclines can undergo redox reactions in mitochondria and generate excessive reactive oxygen species (ROS). Increased production of ROS in cardiomyocytes has deleterious effects on cardiomyocytes: induction of apoptosis through direct DNA damage, mitochondrial dysfunction, upregulation of proinflammatory pathways and altered excitation–contraction coupling through impaired calcium dynamics. There is a dose-relationship between anthracycline administration and cardiomyocyte injury responsible for LV dysfunction and heart failure. As anthracycline-induced cardiac damages are in most cases irreversible, it is of upmost clinical importance to detect them as soon as they appear to limit or stop anthracycline administration and preserve patient’s LV function.