Heart Failure Associated with Sunitinib: Lessons Learned from Animal Models
Mediators, Mechanisms, and Pathways in Tissue Injury (Heinrich Taegtmeyer and Steven A. Atlas, Section Editors)
First Online: 09 August 2011 DOI:
10.1007/s11906-011-0225-8 Cite this article as: Greineder, C.F., Kohnstamm, S. & Ky, B. Curr Hypertens Rep (2011) 13: 436. doi:10.1007/s11906-011-0225-8 Abstract
Sunitinib is a highly potent, multitargeted anticancer agent. However, there is growing clinical evidence that sunitinib induces cardiac dysfunction. Disruption of multiple signaling pathways, which are important in the maintenance of adult cardiac function, is likely to result in cardiovascular toxicity. Basic and translational evidence implicates a potential role for specific growth factor signaling pathways. This review discusses the relevant translational data from animal models of heart failure, focusing on three key pathways that are inhibited by sunitinib: AMP-activated protein kinase (AMPK), platelet-derived growth factor receptors (PDGFRs), and the vascular endothelial growth factor receptors (VEGFRs) 1, 2, and 3. We hypothesize that disruption of these pathways by sunitinib results in cardiotoxicity, and present direct and indirect evidence to support the notion that sunitinib-induced cardiac dysfunction likely involves a variety of molecular mechanisms that are critical for cardiac homeostasis.
Keywords Sunitinib Heart failure Animal models Cardiac dysfunction Cardiotoxicity AMPK PDGFRs VEGFRs Molecular mechanisms References Papers of particular interest, published recently, have been highlighted as: • Of importance
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