The α_v integrin antagonists as novel anticancer agents: an update

Abstract

Integrins are involved in many cellular processes, including some pathological ones associated with various cancers, both solid tumours and metastases. Since integrins are involved in such critical processes as gene expression, which lead to cellular proliferation, migration, survival and angiogenesis, they represent potential targets for therapeutic intervention. The α_vβ₃ integrin is one of the most widely studied integrins because it is one of the most promiscuous. Published studies provide compelling evidence that small molecule antagonists have the potential to treat both solid tumours and metastases, serve as diagnostic imaging agents and be used for site-directed delivery of drugs to solid tumours. The α_vβ₃ integrin antagonists also inhibit blood vessel formation associated with tumour growth. Therapeutic candidates have included antibodies, cyclic peptides, peptidomimetics and small molecules. A number of potent small-molecule antagonists of the α_vβ₃ integrin have now been identified and are progressing in the clinic. This review focuses on the role of α_vβ₃ in cancer. The rationale for the development of the therapeutic and diagnostic candidates based on the key role of α_vβ₃ is discussed.

• αv
• β3
• αv
• β5
• antagonists
• cancer
• integrin