Angiogenesis as a Therapeutic Target in Arthritis: Lessons from Oncology

John      Bainbridge; Branavan      Sivakumar; Ewa      Paleolog

Abstract

Rheumatoid arthritis (RA) is a chronic disabling autoimmune inflammatory disease of unknown aetiology with a prevalence of about 1%in most parts of the world. As a result of the debilitating nature of the disease, sufferers struggle with the simple activities of daily living and frequently fail to remain in full time employment. Furthermore, the mortality associated with the disease is equivalent to that seen in triple vessel coronary artery disease. Over the 10-15 years, advances in understanding the mechanisms of RA pathogenesis based on studies of human cells and animal models of arthritis have led to the identification of new targets for therapeutic intervention. Despite these advances, a significant proportion of patients continue to exhibit disease which is refractory to such therapy. As an alternative to anti-cytokine therapy, formation of new blood vessels (angiogenesis) represents a potentially attractive target for therapy in RA. Angiogenesis has been a putative target in cancer since it was first linked to tumour growth and metastases in the 1970s. A number of significant advances have been made in the development of anti-cancer therapy using such an approach. This review focuses on the potential for targeting angiogenesis in RA, building upon the experience of angiogenesis inhibition in the oncological setting. Through this we hope to emphasise the potential value of anti-angiogenic therapy in RA and identify future directions for optimising treatment of this disabling disease.

Keywords: VEGF, inflammation, chemotherapy, anti-angiogenic therapies, COX-2 inhibitors, Anti-TNF therapy

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