C ellular glue, signaling molecule, cancer accessory — scientists have described various functions for the integrin cellular receptors since the 1970s. And now they may be adding another role to the list: For the first time, an integrin as a target for cancer therapy has made it to a phase III clinical trial. Merck KGaA, based in Germany, is sponsoring the trial to test cilengitide, an RGD (arginine – glycine – aspartic acid) peptide targeting an integrin involved in angiogenesis, for the brain cancer glioblastoma. The study, led by Roger Stupp, M.D., at the University of Lausanne Hospital in Lausanne, Switzerland, is currently recruiting more than 500 patients from Asia, Europe, and North America. “Cilengitide is up front, and if it continues to look good, it will be the fi rst drug of this kind to be approved,” said David Cheresh, Ph.D., at the University of California at San Diego in La Jolla, who worked on the early preclinical studies with the drug. But whether more integrin-targeted drugs will appear remains uncertain. One unanswered question about anti-integrin drugs in general concerns their effects on normal cells. What makes integrins a potentially effective cancer therapy target, their key role in cell survival, also makes them a tricky mark because many of the receptors are active in both normal and cancer cells. Also, some preclinical studies suggest that anti-integrin compounds can promote cancerous activity. “The limitation of these drugs could be toxicity,” said Filippo Giancotti, M.D., Ph.D., at the Sloan – Kettering Institute in New York, who studies integrins in normal development and cancer.