Integrins as therapeutic targets: lessons and opportunities

Integrins — a large family of cell adhesion molecules — have been extensively investigated as targets for diseases including thrombosis, cancer and autoimmune disorders. This article discusses how recent advances in understanding of integrin structure, function, ligand interaction and signalling pathways, as well as lessons learned from first-generation integrin antagonists, are indicating novel strategies for inhibiting integrins that could help exploit their full therapeutic potential. The integrins are a large family of cell adhesion molecules that are essential for the regulation of cell growth and function. The identification of key roles for integrins in a diverse range of diseases, including cancer, infection, thrombosis and autoimmune disorders, has revealed their substantial potential as therapeutic targets. However, so far, pharmacological inhibitors for only three integrins have received marketing approval. This article discusses the structure and function of integrins, their roles in disease and the chequered history of the approved integrin antagonists. Recent advances in the understanding of integrin function, ligand interaction and signalling pathways suggest novel strategies for inhibiting integrin function that could help harness their full potential as therapeutic targets.