Tumors need blood supply to provide them with nutrients and oxygen so as to survive. Cancer cells stimulate new blood vessel growth—a process called tumor angiogenesis to get that supply.
Many attempts have been made to inhibit this process as a means to choke off tumors. But tumor angiogenesis can be sloppy, resulting in immature and malformed blood vessels. Since anti-cancer drugs are carried to tumors by the bloodstream, abnormal blood vessel development also hampers delivery. What if, rather than putting a stop to angiogenesis, we could help tumor blood vessels mature more completely, so tumor-killing therapies could more effectively reach their targets? This counterintuitive concept was proposed several years ago, but researchers lacked a way to do it. Now, in a paper published August 14 in the journal Cancer Cell, researchers at Sanford-Burnham Medical Research Institute (Sanford-Burnham) found a molecule that promotes the tumor vessel maturation process—a discovery that might provide a method for improving cancer drug delivery.
"Our finding suggests that an ability to regulate this molecule could allow us to solve various problems caused by blood vessel abnormalities, including inefficient drug delivery to tumors," said Masanobu Komatsu, Ph.D., associate professor at Sanford-Burnham and senior author of the study.
Previous cancer therapies aimed at tumor angiogenesis were developed with a simple hypothesis: kill the blood vessels that feed a tumor, and tumor cells starve and die. While drugs engineered to slow or halt angiogenesis have been somewhat successful, tumor cells are notoriously adept at surviving in the nutrient and oxygen-deprived environment. So, anti-angiogenic drugs are one possible weapon in medicine's arsenal against tumors, but others are needed.
Komatsu's strategy is based on a new understanding of one particular protein, called R-Ras. He and his team found that R-Ras helps blood vessels mature. The protein is found at high levels in normal, mature blood vessels. Tumor blood vessels, on the other hand, usually have very low R-Ras levels, accounting for their immature nature.
To examine the importance of R-Ras in tumor vessel maturation, Komatsu and his team tried boosting the protein in mice.
"Tumor vessels are chronically immature because they lack R-Ras," said Komatsu. "We found that if we introduce R-Ras there, we are able to normalize the blood vessel in the tumor environment—improving vessel structure and function."