Cancer therapy-associated cardiotoxicity and signaling in the myocardium.
The cardiotoxic potential of cytotoxic cancer chemotherapy is well known. Prime examples are the anthracyclines, which are highly efficacious agents for hemopoietic malignancies and solid tumors, but their clinical use is limited primarily by cardiotoxicity. Besides the conventional chemotherapeutics, new cancer drugs were developed in the last decade with the goal to specifically inhibit selected molecular targets such as growth factor receptors or intracellular tyrosine kinases in cancer cells. However, the outcome of combining conventional and newer cancer therapies could have unexpected side effects not anticipated so far and the long-term outcome is not known. Sometimes, however, unexpected side effects also shed light on previously unknown physiological functions. For example, the anti-HER2 cancer therapeutic trastuzumab (Herceptin), which can induce cardiac dysfunction, has demonstrated the importance of the ErbB/neuregulin signaling system in the adult heart. Subsequently, the role of endothelial-myocardial communication in maintaining phenotype and survival of adult cardiomyocytes has increasingly been recognized.
Zuppinger
Christian
C
Swiss Cardiovascular Center, Inselspital, Bern University Hospital, Bern, Switzerland. christian.zuppinger@insel.ch
Suter
Thomas M
TM
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D018943:Anthracyclines / Q000009:adverse effects; D000911:Antibodies, Monoclonal / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000009:adverse effects*; D000072237:ERG1 Potassium Channel; D066246:ErbB Receptors / Q000502:physiology; D051638:Ether-A-Go-Go Potassium Channels / Q000037:antagonists & inhibitors; D006331:Heart Diseases / Q000139:chemically induced*; D006801:Humans; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D009369:Neoplasms / Q000098:blood supply / Q000188:drug therapy; D020890:Neuregulin-1 / Q000502:physiology; D020880:Neuregulins / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000502:physiology; D066247:Receptor, ErbB-4; D015398:Signal Transduction; D000068878:Trastuzumab
D020533:Angiogenesis Inhibitors; D018943:Anthracyclines; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D000072237:ERG1 Potassium Channel; D066246:ErbB Receptors; D051638:Ether-A-Go-Go Potassium Channels; D020890:Neuregulin-1; D020880:Neuregulins; D018719:Erb-b2 Receptor Tyrosine Kinases; D066247:Receptor, ErbB-4; D000068878:Trastuzumab; C117467:neuregulin beta; C587689:ERBB4 protein, human