The clinical manipulation of angiogenesis: pathology, side-effects, surprises, and opportunities with novel human therapies

The first phase of angiogenesis research has provided knowledge of the basic pathobiology of angiogenesis and its manipulation in models, mouse, and man. The first line of therapeutic substances has been devised and is now in clinical trials. New lessons are being learned from clinical observations. Unexpected side-effects are being noted, particularly affecting the nervous system. Other side-effects may be anticipated from a sound knowledge of clinical pathology and recognition of the commonality of angiogenesis to multiple disease mechanisms, but these may be tolerable or avoidable. Angiogenesis researchers await further feedback and ideas from the clinic to stimulate the next phase of basic and applied research.