 A team of researchers has designed a new protein that targets a cell surface receptor linked to various diseases. Its ability to effectively bring the receptor's harmful activity to a halt, without damaging surrounding tissues, makes the protein a promising therapeutic agent for treating a host of diseases, including cancer. Created from a human protein, proagios selectively targets a cell surface receptor called Integren Alpha V Beta 3. Integrens are a family of glue-like proteins that help stabilize the structure of cells within their surrounding environment and help cells communicate to the outside world and vice versa. But studies show that abnormally high levels of otherwise benign proteins like Integren Alpha V Beta 3 are expressed in cells affected by pathological disorders. Disorders such as skin fibrosis, a serious disease characterized by the inflammation and hardening of the skin, rheumatoid arthritis, and metastatic cancer. Integren Alpha V Beta 3 has therefore long been in the sights of scientists looking to develop potent drugs that prevent inflammation and the formation of new blood vessels. What sets proagio apart from other protein drugs is the way it binds to Integren Alpha V Beta 3. Other drugs commonly target what is called the ligand binding site of the Integren. Binding to this site generally disrupts the adhesion function of Integren Alpha V Beta 3, causing cells to detach from their surroundings and ideally wither away. But because the signaling function of the Integren typically remains intact, cells may continue to promote harmful inflammatory responses, limiting the clinical success of the ligand-based approach. Proagio is designed to bind to a different site of Integren Alpha V Beta 3 to produce an entirely different response. The protein's unique binding mechanism enables it to recruit and activate an enzyme called Caspace-8, which plays an essential role in programmed cell death. Using mouse models, the research team showed that enlisting the help of Caspace-8 makes proagio much more effective than ligand binding proteins in preventing the formation of new blood vessels. It's this ability to cut off the supply of blood that also makes proagio more effective in stopping the growth of tumors. The researchers showed that tumors introduced into proagio-treated mice showed dramatic reductions in vessel density and vessel length and in the number of branch points. And because proagio is programmed to bind strongly to a specific region of Integren Alpha V Beta 3, the protein's anti-cancer effects are highly selective. Proagio showed no adverse effects on the blood vessels of surrounding healthy tissue. The researchers admit that it is not entirely understood how or why proagio's unique binding mechanism produces such dramatically different results from those of proteins that lock into a nearby site on the same Integren. But they suggest that proagio's strong and highly targeted effects make it a promising candidate for clinical development in the fight against cancer and a range of other diseases.