title: Hypertension induced by vascular endothelial growth factor signaling pathway inhibition: mechanisms and potential use as a biomarker.
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.
authors.affiliation: Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Emily S
authors.initials: ES
authors.lastname: Robinson
authors.forename: Eliyahu V
authors.initials: EV
authors.lastname: Khankin
authors.forename: S Ananth
authors.initials: SA
authors.lastname: Karumanchi
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Humphreys
mesh_terms: D020533:Angiogenesis Inhibitors / Q000009:adverse effects* / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D015415:Biomarkers; D045462:Endothelium-Dependent Relaxing Factors / Q000037:antagonists & inhibitors; D006801:Humans; D006973:Hypertension / Q000139:chemically induced* / Q000503:physiopathology; D009318:Natriuresis; D009369:Neoplasms / Q000188:drug therapy; D012084:Renin-Angiotensin System; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000187:drug effects / Q000502:physiology*
chemical_list: D020533:Angiogenesis Inhibitors; D015415:Biomarkers; D045462:Endothelium-Dependent Relaxing Factors; D042461:Vascular Endothelial Growth Factor A