This in turn can make tumors more susceptible to chemotherapy, according to Nature paper.

Investigators at the Moores Cancer Center at the University of California, San Diego report that methods to block VEGF in tumors don’t really halt blood-vessel formation in the tumors. Instead they actually enable vessels to mature.

Yet while this counter-intuitive action initially helps the tumor grow larger, it also provides a better conduit for chemotherapeutic drugs and makes the tumor more susceptible to them, they add. The researchers say the findings provide an explanation for recent evidence showing that anti-angiogenesis drugs such as Avastin can be much more effective when combined with chemotherapy.

The team mimicked the action of anti-angiogenesis drugs by genetically reducing VEGF levels in mouse tumors and inflammatory cells in various cancers. They also used drugs to inhibit VEGF receptor activity. In every case, blood vessels were made normal again.

They found that receptors for VEGF and another growth-promoting protein, PDGF, form a complex that turns off PDGF and the activity of the blood-vessel support cells called pericytes. Tumors make too much VEGF in their haste to form blood vessels, which turns on the receptor complex. Cutting VEGF levels in the tumor in turn increases the activity of pericytes that surround the blood vessels, stabilizing them and making them more sensitive to chemotherapy, the scientists explain.

A related study showed that tumors were more vulnerable to drugs after inflammatory cells lost the ability to express VEGF. The findings may provide a new strategy for treating cancer, says David Cheresh, Ph.D., professor and vice chair of pathology at the UC San Diego School of Medicine and the Moores UCSD Cancer Center. “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 article appears in the November 9 online version of Nature.

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