Brigham and Women's Hospital, Boston, Massachusetts, USA.
Semin Nephrol. 2010 Nov;30(6):591-601. doi: 10.1016/j.semnephrol.2010.09.007.
Drugs that inhibit the vascular endothelial growth factor (VEGF) signaling pathway are a rapidly growing chemotherapy class for treatment of solid tumors. This targeted therapy is more specific than traditional chemotherapy, causing fewer side effects. However, VEGF-targeted therapies cause hypertension in 30% to 80% of patients. Unlike traditional off-target side effects, hypertension is a mechanism-dependent, on-target toxicity, reflecting effective inhibition of the VEGF signaling pathway rather than nonspecific effects on unrelated signaling pathways. In this article, we review current understanding of the mechanisms of VEGF-targeted therapy-induced hypertension, discuss similarities with preeclampsia, review implications for therapy of this increasingly common clinical problem, and discuss the potential use of blood pressure increase as a biomarker for proper drug dosing and effective VEGF pathway inhibition.
抑制血管内皮生长因子（VEGF）信号通路的药物是治疗实体瘤的一类快速发展的化疗药物。与传统化疗相比，这种靶向治疗更具特异性，副作用更少。然而，VEGF 靶向治疗会导致 30%至 80%的患者发生高血压。与传统的脱靶副作用不同，高血压是一种机制依赖性的靶毒性，反映了对 VEGF 信号通路的有效抑制，而不是对无关信号通路的非特异性影响。在本文中，我们综述了目前对 VEGF 靶向治疗引起高血压的机制的认识，讨论了与子痫前期的相似之处，综述了对这一日益常见的临床问题的治疗意义，并讨论了将血压升高用作适当药物剂量和有效 VEGF 通路抑制的生物标志物的潜在用途。
