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Comment
. 2009 Oct 1;15(19):5947-9.
doi: 10.1158/1078-0432.CCR-09-1717. Epub 2009 Sep 29.

Rapid development of hypertension by sorafenib: toxicity or target?

Benjamin D Humphreys  1 , Michael B Atkins
Affiliations
Comment

Rapid development of hypertension by sorafenib: toxicity or target?

Benjamin D Humphreys et al. Clin Cancer Res. .

Abstract

Blood pressure elevation is likely a pharmacodynamic marker of VEGF signaling pathway (VSP) inhibition and could be useful for optimizing safe and effective VSP inhibitor dosing. Blood pressure rises on the first day of treatment, facilitating design and interpretation of future trials aiming to correlate blood pressure changes with clinical outcomes.

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Figures

Figure 1
Figure 1. Mechanisms of VSP inhibitor-induced hypertension
Polymorphisms in the VEGF gene might alter VEGF expression or signaling, thereby determining risk of HTN, anti-tumor efficacy or both during treatment with VSP inhibitors. VSP inhibition by sorafenib removes an endothelial cell survival signal, leading to apoptosis and capillary rarefaction. It also decreases eNOS expression and activity, inhibiting endothelial cell-derived NO, causing vascular smooth muscle cell constriction. Both capillary rarefaction and vasoconstriction lead to increased systemic vascular resistance and elevated BP.
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References

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