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Semin Nephrol. 2010 Nov;30(6):591-601. doi: 10.1016/j.semnephrol.2010.09.007.

Hypertension induced by vascular endothelial growth factor signaling pathway inhibition: mechanisms and potential use as a biomarker.

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Brigham and Women's Hospital, Boston, Massachusetts, USA.


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.

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