Strengthening Tumor Blood Vessels Could Improve Delivery of Anticancer Drugs

Since poor blood circulation to tumors may mean that anticancer drugs fail to reach their target in high enough concentration to be effective, some cancer researchers are suggesting a radical approach to normalize tumor blood supply.

Cancer cells usually trigger the process of angiogenesis, the formation of new blood vessels, but the result is often immature and malformed blood vessels. Since anticancer drugs are carried to tumors by the bloodstream, abnormal blood vessel development can reduce the effectiveness of chemotherapy.

Investigators at the Sanford-Burnham Medical Research Institute (Orlando, FL, USA) have searched for a way to strengthen the tumor vascular system to improve the chances for anticancer drugs to reach their target cells.

They reported in the August 14, 2012, issue of the journal Cancer Cell that R-Ras, a small GTPase of the Ras family, was essential for the establishment of mature, functional blood vessels in tumors. The genetic disruption of R-Ras severely impaired the maturation processes of tumor vessels in mice. Conversely, the gain of function of R-Ras improved vessel structure and blood perfusion and blocked plasma leakage by enhanced endothelial barrier function. R-Ras 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.

"Tumor vessels are chronically immature because they lack R-Ras," said senior author Dr. Masanobu Komatsu, associate professor in the tumor microenvironment program at the Sanford-Burnham Medical Research Institute. "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."

"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 Dr. Komatsu. "Our discovery provided a better understanding of blood vessel formation process and may prompt researchers to rethink how this process may be controlled to improve human health."

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Sanford-Burnham Medical Research Institute