In the past, blood vessels were considered to be a simple system of conduits
that did little more than provide oxygen and nutrients to maintain cellular functions within different tissues.Recent studies of the biochemistry and cell biology of the vessel wall, however, have dramatically extended the role of the vasculature, which is now believed to directly regulate the development and function of certain organs. Thus, the identification and characterization of the genes that govern vascular functions within various organs may be beneficial for the treatment of disease processes.Angiogenesis refers to the process by which new blood vessels are formed within the body. When tissues need more oxygen, for example, they release molecules, such as VEGF, that encourage blood vessels to grow.
Vascular endothelial growth factor (VEGF) was identified as a major regulator of vascular functions. VEGF is a key player in a broad variety of biological processes, including embryonic development, reproductive functions, growth of the long bones in the body, and the generation of blood cells.
Angiogenesis and Cancer
Progressive tumor growth is dependent on angiogenesis. Most tumors in humans persist in situ for a long period of time (from months to years) in an avascular, quiescent status. In this phase the tumor may contain a few million cells. When a subgroup of cells within the tumor switches to an angiogenic phenotype by changing the local equilibrium between positive and negative regulators of angiogenesis, the tumor starts to grow rapidly and becomes clinically detectable. The ability to inhibit angiogenesis and turn off the blood supply to tumors could potentially lead to a new generation of cancer therapies.
The VEGF protein is a key mediator of tumor angiogenesis. Interference with VEGF activity by means of a neutralizing antibody can reduce tumor growth and metastasis. Studies led to the development of a humanized anti-VEGF antibody, Avastin™ (bevacizumab) as a therapy for solid tumors. Avastin received U.S. Food and Drug Administration approval in February 2004 for use in combination with intravenous 5-Fluorouracil-based chemotherapy as a treatment for first-line metastatic colorectal cancer. Studies on the role of VEGF in intraocular neovascularization also initiated clinical development of an anti-VEGF antibody fragment as a therapy for wet age-related macular degeneration, Lucentis™ (ranibizumab).