Current Hypertension Reports

, Volume 13, Issue 6, pp 436–441

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)

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

SunitinibHeart failureAnimal modelsCardiac dysfunctionCardiotoxicityAMPKPDGFRsVEGFRsMolecular mechanisms

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Colin F. Greineder
    • 1
  • Sarah Kohnstamm
    • 2
  • Bonnie Ky
    • 3
  1. 1.Department of Pharmacology, Institute for Translational Medicine and Therapeutics, Department of Emergency MedicineUniversity of Pennsylvania School of MedicinePhiladelphiaUSA
  2. 2.Division of Cardiovascular MedicineUniversity of Pennsylvania School of MedicinePhiladelphiaUSA
  3. 3.Division of Cardiovascular Medicine, Center for Clinical Epidemiology and BiostatisticsUniversity of Pennsylvania School of MedicinePhiladelphiaUSA