抄録
Tyrosine kinase inhibitors (TKIs) have dramatically improved anticancer therapy. However, cardiotoxicity of a TKI was firstly reported for trastuzumab, a monoclonal antibody directed against ERBB2 receptors in 2001. In addition, imatinib, a small-molecule inhibitor of the fusion protein Bcr-Abl, was reported to cause severe congestive heart failure. Sunitinib, a multitargeted TKI, being developed for renal cell carcinoma and gastrointestinal stromal tumor in Japan, also has been claimed its causal relationship with heart failure, left ventricular dysfunction and hypertension based on a small, retrospective analysis. Force et al. (2007) recently reviewed basic mechanisms through which those TKIs interrupt specific signaling pathways that would lead to cardiomyocyte dysfunction and/or death and claimed that multitargeted TKIs, e.g., sunitinib, may possess higher potential of cardiotoxicity. One of major mechanisms of the cardiotoxicity is postulated to be mitochondrial dysfunction. Dykens et al. (2008), however, showed that sunitinib had minimal effects on respiration only at concentrations greatly exceeding therapeutic levels. In addition, Blasi et al. (2008) reported that sunitinib-induced elevation in blood pressure in rats was accompanied with no cardiac structure and mitigated by a calcium channel blocker. Thus, further investigation is needed to understand the cardiotoxicity of TKIs. In addition, careful risk-benefit analysis would be highly recommended.
