Beyond antiangiogenesis: vascular modulation as an anticancer therapy-a review.

This review attempts to move beyond the traditional borders of antiangiogenesis and toward the dynamic, evolving strategies of vascular modulation. This repositioning entails a two-fold paradigm shift: conceptually, to a view of antiangiogenesis as only one part of a larger story, and therapeutically, to approaches which attempt to modulate tumor blood flow instead of simply inhibiting it. Three vascular modulation strategies-provascular, antivascular, and redistributive-are presented with representative compounds. These vascular modulation strategies are described in specific measurable characteristics (blood vessel maturity and type, effect on blood flow, microenvironmental target, molecular target, angiogenic biomarker, and imaging biomarkers) that will help define the tumor types that are more susceptible to a particular vascular modulation strategy thereby guiding therapeutic agent selection and enabling a personalized medicine approach.