Angiogenesis Protocols

M E T H O D S I N M O L E C U L A R M E D I C I N E TM Angiogenesis Protocols Edited by by Edited J. Clifford Murray Humana Press Therapeutic Inhibition 3 1 Therapeutic Inhibition of Angiogenesis Hua-Tang Zhang and Roy Bicknell 1. Introduction The idea of antiangiogenesis as a therapeutic strategy has been around for several decades (1). Vigorously pursued as a novel anticancer strategy (reviewed in (2–6), it is now widely considered to be a promising approach to the treatment of a range of pathologies of which uncontrolled vascular proliferation is a component (see Table 1). To date, therapeutic benefit has been achieved with antiangiogenic therapy in the treatment of life-threatening infantile hemangioma, pulmonary hemangiomatosis, and in the treatment of some vascular tumors (7,8). Recent advances in the field of antiangiogenesis and vascular targeting include: (1) the discovery of two novel natural endogenous angiogenic inhibitors, called angiostatin and endostatin (9,10), (2) the demonstration that in three mouse xenograft models, cycled endostatin therapy showed no evidence for acquired drug resistance but induced several wave-like regression– regrowth–regression cycles followed by indefinite tumor dormancy (11), (3) destruction of tumor endothelium and induction of tumor infarction by selective clotting in tumor vessels (12), and (4) in vitro and in vivo selection of peptides that bind to endothelium in an organ-specific and tumor-selective fashion (13,14). The latter was followed by successful targeted delivery of pep