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

Emily S. Robinson, Eliyahu V. Khankin, S. Ananth Karumanchi, Benjamin D. Humphreys

Research output: Contribution to journalArticlepeer-review

136 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)591-601
Number of pages11
JournalSeminars in Nephrology
Volume30
Issue number6
DOIs
StatePublished - Nov 2010

Keywords

  • Hypertension
  • Nitric oxide
  • Targeted therapy
  • Thrombotic microangiopathy
  • VEGF

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