Integrins are a large family of dimeric receptors composed by alpha and beta 
subunits that, once bound to extra-cellular matrix (ECM) proteins, regulate a 
variety of cellular processes such as cell motility, migration, and 
proliferation. The integrins transduce signals from inside-out and outside-in 
the cell, thus representing the cellular link to the external environment. For 
these properties, integrin activation has been involved in pathological 
processes like tumor growth and metastasis formation. Recent advances in the 
elucidation of the crystallographic structures of the alphavbeta3 and 
alphaIIbeta3 integrins are promoting studies focused to the search of small 
molecule antagonists that can block the integrin binding to ECM and inhibit the 
biological effects exerted by these receptors. In this review we will focus on 
small molecule antagonists of alphavbeta3 and alphavbeta5 integrin as tools for 
cancer therapy while other integrins will only be briefly mentioned. Cilengitide 
(cyclic peptidic alphavbeta3 and alphavbeta5 antagonist) is currently in 
clinical trials for anti cancer therapy. Combination of integrin alphavbeta3 
antagonists and other traditional therapeutic approaches may represent a future 
strategy to inhibit tumor growth and metastasis spreading.