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Angiogenesis

Angiogenesis is the process of new blood vessel development. The process occurs during normal physiological conditions such as wound healing and embryonic development and in pathological conditions such as athersosclerosis, diabetic retinopathy and cancer.

Angiogenesis is regulated by a balance of pro and anti-angiogenic growth factors and is activated when the balance is in favour of the pro- angiogenic factors. During the process of angiogenesis tumours produce and release growth factors that bind to receptors located on the endothelial cells of nearby blood vessels. The endothelial cells become activated and produce enzymes which degrade the basement membrane of existing blood vessels. The endothelial cells then divide and migrate toward the tumour. The cells form tubes that connect to form loops that allow blood flow. Muscle cells then stabilise the newly formed vessels.

Angiogenesis is necessary for the growth of primary tumours beyond a size of 1-2mm. It is a key event in the formation of metastasis whereby tumours can grow from a secondary site. Different cancers metastasise to different sites, for blood-borne cells the liver is a common site of metastasis. Breast or prostate cancers can metastasise to the bone. The presence of metastasis is accompanied by a poorer prognosis. There is difficulty treating metastasis with the same treatments used for confined disease. As angiogenesis is essential for tumour growth (and metastasis) many research efforts are focusing to control tumour growth by targeting the blood supply.

Anti-angiogenic therapy is designed to prevent the process of new blood vessel development. There are several anti-angiogenic strategies under research including; inhibitors of matrix metalloproteinases, blockers of angiogenic growth factors, inhibitors of endothelial cell migration and proliferation and agents with unspecific mechanism of action. Anti-angiogenic therapy is a proven mode of therapy with beneficial effects observed using a combination regime in cancer or as a monotherapy for macular degeneration.