Combination therapy for ocular and tumor angiogenesis

Abstract

Evaluation of: Dorrell MI, Aguilar E, Scheppeke L, Barnett FH, Friedlander M. Combination angiostatic therapy completely inhibits ocular and tumor angiogenesis. Proc. Natl Acad. Sci. USA 104, 967–972 (2007).

This series of studies evaluates the activity of three angiostatic compounds that target various angiogenic processes, including vascular endothelial growth factor (VEGF), extracellular endothelial cell survival and endothelial intracellular adhesion and lumen formation. The compounds are studied alone and in combination, in animal models of retinal neovascularization (both developmental and pathological) and in tumor vasculature. Angiostatic monotherapy resulted in the upregulation of proangiogenic factors, while combination therapy resulted in significantly less upregulation. Angiostatic combination therapy had synergistic angiostatic and antineovascular effects in retinal models, obliterated tumor vasculature and prolonged survival, and did not affect normal vasculature in any model. These studies point to the utility of combination therapy in the clinic. Even though anti-VEGF therapy is currently the only available angiostatic therapy for ocular choroidal neovascularization, these studies support the concept of combination therapy using agents with different mechanisms of action.

Keywords::

• age-related macular degeneration
• angiogenesis
• angiostasis
• bevacizumab
• choroidal neovascularization
• combination therapy
• gliosarcoma
• monotherapy
• pegaptanib
• ranibizumab
• retinopathy
• vascular endothelial growth factor
• verteporfin photodynamic therapy