Cilengitide (EMD 121974), a cyclized Arg-Gly-Glu(RGD)-containing pentapeptide that selectively blocks activation of the αvβ3 and αvβ5 integrins has shown encouraging activity in patients with glioblastoma as single agent, and in association with standard RT and temozolomide. Cilengitide has both anti-angiogenic and direct anti-tumor effects and is a possible alternative to TNF in isolated limb perfusion. Cilengitide is the most clinically advanced and is emerging as a prototype for this class of anticancer therapy.