Molecular mechanisms of cardiotoxicity of tyrosine kinase inhibition.
Cancer therapy has progressed remarkably in recent years. In no area has this been more apparent than in the development of "targeted therapies", particularly those using drugs that inhibit the activity of certain tyrosine kinases, activating mutations or amplifications of which are causal, or strongly contributory, to tumorigenesis. However, some of these therapies have been associated with toxicity to the heart. Here we summarize what is known about the cardiotoxicity of cancer drugs that target tyrosine kinases. We focus on basic mechanisms through which interruption of specific signalling pathways leads to cardiomyocyte dysfunction and/or death, and contrast this with therapeutic responses in cancer cells.
Force
Thomas
T
Center for Translational Medicine and Cardiology Division, Department of Medicine, Thomas Jefferson University, 1025 Walnut Street, Philadelphia, PA 19107, USA. thomas.force@jefferson.edu
Krause
Daniela S
DS
Van Etten
Richard A
RA
D048868:Adaptor Proteins, Signal Transducing / Q000037:antagonists & inhibitors; D000911:Antibodies, Monoclonal / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D001557:Benzenesulfonates / Q000009:adverse effects; D016503:Drug Delivery Systems; D004791:Enzyme Inhibitors / Q000009:adverse effects; D006321:Heart / Q000254:growth & development / Q000502:physiology; D006331:Heart Diseases / Q000139:chemically induced*; D006801:Humans; D007211:Indoles / Q000009:adverse effects; D000077341:Lapatinib; D008954:Models, Biological; D009369:Neoplasms / Q000188:drug therapy*; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors / Q000009:adverse effects*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D016315:Proto-Oncogene Proteins c-abl / Q000037:antagonists & inhibitors; D011725:Pyridines / Q000009:adverse effects; D011758:Pyrroles / Q000009:adverse effects; D011799:Quinazolines / Q000009:adverse effects; D000077157:Sorafenib; D000077210:Sunitinib; D000068878:Trastuzumab
D048868:Adaptor Proteins, Signal Transducing; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D001557:Benzenesulfonates; C413364:ERBIN protein, human; D004791:Enzyme Inhibitors; D007211:Indoles; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D011758:Pyrroles; D011799:Quinazolines; D000077341:Lapatinib; D009536:Niacinamide; D000077157:Sorafenib; D011505:Protein-Tyrosine Kinases; D016315:Proto-Oncogene Proteins c-abl; D000068878:Trastuzumab; D000077210:Sunitinib