title: Complications of chemotherapy, a basic science update.
abstract: Anthracyclines, discovered 50 years ago, are antibiotics widely used as antineoplastic agents and are among the most successful anticancer therapies ever developed to treat a wide range of cancers, including hematological malignancies, soft tissue sarcomas and solid tumors. However, some anthracyclines, including doxorubicin, exhibit major signs of cardiotoxicity that may ultimately lead to heart failure (HF). Despite intensive research on doxorubicine-induced cardiotoxicity, the underlying mechanisms responsible for doxorubicin-induced cardiotoxicity have not been fully elucidated yet. Published literature so far has focused mostly on mitochondria dysfunction with consequent oxidative stress, Ca(2+) overload, and cardiomyocyte death as doxorubicin side effects, leading to heart dysfunction. This review focuses on the current understanding of the molecular mechanisms underlying doxorubicin-induced cardiomyocyte death (i.e.: cardiomyocyte death, mitochondria metabolism and bioenergetic alteration), but we will also point to new directions of possible mechanisms, suggesting potent prior or concomitant alterations of specific signaling pathways with molecular actors directly targeted by the anticancer drugs itself (i.e. calcium homeostasis or cAMP signaling cascade). The mechanisms of anticancer cardiac toxicity may be more complex than just mitochondria dysfunction. Partnership of both basic and clinical research is needed to promote new strategies in diagnosis, therapies with concomitant cardioprotection in order to achieve cancer treatment with acceptable cardiotoxicity along life span.
authors: Inserm UMR-S 769, LabEx Lermit-DHU Torino, université Paris-Sud, faculté de pharmacie, signalisation et physiopathologie cardiaque, 92296 Châtenay-Malabry cedex, France.
authors: Marianne
authors: M
authors: Mazevet
authors: Maryline
authors: M
authors: Moulin
authors: Anna
authors: A
authors: Llach-Martinez
authors: Cyrus
authors: C
authors: Chargari
authors: Eric
authors: E
authors: Deutsch
authors: Ana-Maria
authors: AM
authors: Gomez
authors: Eric
authors: E
authors: Morel
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000009:adverse effects*; D020013:Calcium Signaling / Q000187:drug effects; D054715:Cardiotoxins / Q000009:adverse effects*; D016923:Cell Death / Q000187:drug effects; D000242:Cyclic AMP / Q000502:physiology; D004317:Doxorubicin / Q000009:adverse effects*; D006333:Heart Failure / Q000139:chemically induced*; D006801:Humans; D008929:Mitochondria, Heart / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000187:drug effects; D018384:Oxidative Stress / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000903:Antibiotics, Antineoplastic; D054715:Cardiotoxins; D004317:Doxorubicin; D000242:Cyclic AMP