Department of Pharmacology, Institute for Translational Medicine and Therapeutics, Department of Emergency Medicine, University of Pennsylvania School of Medicine, 3400 Spruce Street, Philadelphia, PA 19104, USA.
Curr Hypertens Rep. 2011 Dec;13(6):436-41. doi: 10.1007/s11906-011-0225-8.
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.
舒尼替尼是一种高效能、多靶点的抗癌药物。然而，越来越多的临床证据表明舒尼替尼可导致心脏功能障碍。破坏在维持成人心脏功能方面起重要作用的多个信号通路可能导致心血管毒性。基础和转化证据表明特定生长因子信号通路可能起作用。本文讨论了心力衰竭动物模型中的相关转化数据，重点关注舒尼替尼抑制的三个关键通路：AMP 激活的蛋白激酶 (AMPK)、血小板衍生生长因子受体 (PDGFRs) 和血管内皮生长因子受体 (VEGFRs)1、2 和 3。我们假设舒尼替尼对这些通路的破坏导致心脏毒性，并提出直接和间接证据支持舒尼替尼诱导的心脏功能障碍可能涉及多种对心脏稳态至关重要的分子机制的观点。
