Drugs designed to block blood vessel growth may aid anti-cancer drug delivery
TUESDAY 11 NOVEMBER 2008
New US research has added more weight to the theory that drugs designed to block the growth of blood vessels required for tumour growth could actually stabilise existing tumour blood vessels and improve the delivery of anti-cancer drugs.
In order to survive and grow, tumours need to produce new blood vessels so that they can obtain blood and oxygen.
Anti-angiogenic drugs, such as Avastin, are designed to stop this process by blocking the production of vascular endothelial growth factor (VEGF), a protein required for blood vessel growth.
We may be giving the right drugs, but we may not be giving them in the right order.
- Dr David Cheresh, Moores UCSD Cancer Centre
However, scientists are finding evidence that blocking the VEGF protein may help to stabilise and even strengthen existing tumour blood vessels, allowing drugs to penetrate into the heart of the cancer.
The researchers at the University of California San Diego's Moores Cancer Centre noted that by supporting these existing blood vessels, anti-angiogenesis drugs help to make tumours more vulnerable to the effects of chemotherapy drugs, which reach tumours via the bloodstream.
Dr David Cheresh, professor and vice chair of pathology at the UCSD School of Medicine and the Moores UCSD Cancer Centre, said: "We've discovered that when anti-angiogenesis drugs are used to lower the level of VEGF within a tumour, it's not so much a reduction in the endothelial cells and losing blood vessels as it is an activation of the tumour blood vessels supporting cells.
"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."
In a study published in Nature, the researchers engineered mice with low VEGF levels to mimic the action of anti-angiogenic drugs. They also gave the mice drugs to inhibit the activity of VEGF receptors.
The reduction in VEGF levels was found to increase the activity of cells called pericytes which surround the blood vessels.
This in turn helps to stabilise the blood vessels - which are usually built poorly in tumours - so that they become healthier and more 'normal'.
According to Dr Cheresh, the findings may help to explain recent studies which have shown anti-angiogenic drugs to be more effective when combined with chemotherapy.
He said: "It means that chemotherapy could be timed appropriately. We could first stabilise the blood vessels, and then come in with chemotherapy drugs that are able to treat the cancer."
The scientist suggested that existing treatment regimes may need to be restructured in order to improve their effectiveness.
"We may be giving the right drugs, but we may not be giving them in the right order. We're just beginning to understand how it works," he added.
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