Anti-cancer Drugs Help in Building, Not Destroying Blood Vessels

by VR Sreeraman on Nov 10 2008 4:02 PM

Scientists have now discovered that anti-cancer drugs, earlier believed to tear down blood vessels, actually help in building stronger and more normal blood vessels.

Previously it was believed that it was possible to cease angiogenesis, a process in which tumour generates blood vessels to feed its growth, by creating drugs targeting at stopping a key vessel growth-promoting protein, called VEGF, or vascular endothelial growth factor.

But now, researchers at the Moores Cancer Center at the University of California, San Diego (UCSD) in La Jolla have found evidence that blocking VEGF may not really halt the process, but would in turn lead to the production of more blood vessels that are not only stronger, but more normal and larger also.

Thus, the tumour becomes more susceptible to the effects of chemotherapy drugs.

Led by Dr. David Cheresh, professor and vice chair of pathology at the UC San Diego School of Medicine, the researchers mimicked the action of anti-angiogenesis drugs by genetically reducing VEGF levels in mouse tumours and inflammatory cells in various cancers, including pancreatic cancer.

The scientists also used drugs to inhibit VEGF receptor activity.

It was discovered that in all the cases, blood vessels were made normal again.

In their opinion, the results may explain recent evidence showing that anti-angiogenesis drugs such as Avastin, when combined with chemotherapy can turn out to be much more effective.

The findings of the study may pave the way for better treatment strategies for a variety of cancers.

"We've discovered that when anti-angiogenesis drugs are used to lower the level of VEGF within a tumor, it's not so much a reduction in the endothelial cells and losing blood vessels as it is an activation of the tumor blood vessels supporting cells," Nature magazine quoted Cheresh as saying.

"This enables vessels to mature, providing a conduit for better drug delivery to the tumour. While the tumours initially get larger, they are significantly more sensitive to chemotherapeutic drugs."

Thus, according to Cheresh, the findings may provide a new strategy for treating cancer.

He added: "It means that chemotherapy could be timed appropriately. We could first stabilize the blood vessels, and then come in with chemotherapy drugs that are able to treat the cancer."

The researchers also demonstrated that tumours were more susceptible to drugs after inflammatory cells lost the ability to express VEGF.

"These two papers define a new mechanism of action for VEGF and for anti-angiogenesis drugs. It appears that the drugs, in shutting down VEGF activity, are actively maturing blood vessels, causing them to become stable and more normal, as opposed to reducing blood vessels," said Cheresh.

The study has been published in the online edition of the journal Nature.