TY - JOUR
T1 - Hypertension induced by vascular endothelial growth factor signaling pathway inhibition
T2 - Mechanisms and potential use as a biomarker
AU - Robinson, Emily S.
AU - Khankin, Eliyahu V.
AU - Karumanchi, S. Ananth
AU - Humphreys, Benjamin D.
PY - 2010/11
Y1 - 2010/11
N2 - 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.
AB - 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.
KW - Hypertension
KW - Nitric oxide
KW - Targeted therapy
KW - Thrombotic microangiopathy
KW - VEGF
UR - http://www.scopus.com/inward/record.url?scp=78649953614&partnerID=8YFLogxK
U2 - 10.1016/j.semnephrol.2010.09.007
DO - 10.1016/j.semnephrol.2010.09.007
M3 - Article
C2 - 21146124
AN - SCOPUS:78649953614
SN - 0270-9295
VL - 30
SP - 591
EP - 601
JO - Seminars in Nephrology
JF - Seminars in Nephrology
IS - 6
ER -