Beta3-Integrin Protein Possible Key to Block Tumor Growth

A protein that has been at the forefront of cancer drug development for the last 20 years should not be given up on according to new findings by British investigators.

The most advanced version of αvβ3-integrin antagonists was unsuccessful in clinical trials to treat aggressive forms of brain cancer. However, research published January 3, 2014, in the American Heart Association’s journal Circulation Research revealed that targeting the specific protein could still be key to blocking tumor growth. Most significantly, the drugs targeting the protein cause minimal side effects compared to other drugs, which can cause high blood pressure and bleeding in the gut.


Tumors must recruit their own blood supply to grow beyond a very small size. The researchers examined the cells that line blood vessels (endothelial cells) in mice, and specifically the role of a widely expressed protein called beta3-integrin.

Dr. Stephen Robinson, from the University of East Anglia’s (UEA; Norwich, UK) School of Biological Sciences, said, “This protein has been the focus of drug design over the last two decades because its expression is vastly increased in endothelial cells during blood vessel recruitment. The most advanced of these drugs, however, has recently failed a phase III clinical trial to treat an aggressive form of brain cancer. In line with other clinical work, patients respond to treatment for a short while but then their cancers escape the treatment. This research helps to explain why these very promising drugs aren’t meeting with the success that was anticipated and it suggests a way forward—how to make them work better.”

The study authors additionally reported that they revealed how tumors continue to grow in spite of treatment that should suppress blood vessel recruitment. In this study, they modulated how they are recruiting their blood vessels by using a different pathway from the one that is being targeted. They have identified some molecular alterations in endothelial cells that occur with long-term suppression of beta3-integrin that might help the cells evade the beta3-integrin blockade.

Dr. Robinson continued, “Our research also shows that timing is critical when targeting the protein beta3-integrin. Importantly, these findings have reestablished the expression of beta3-integrin as a valid clinical target when treating cancer. Efforts must now be refocused to either develop new drugs to target beta3-integrin, or figure out how to more effectively use the drugs that already exist.”

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University of East Anglia