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Discovery may make chemotherapy more effective against pancreatic cancer.

20 March 2012

Two research groups have simultaneously discovered why chemotherapy has little effect against pancreatic cancer and have developed a novel treatment to increase its effectiveness.

Researchers at Cancer Research UK’s Cambridge Research Institute and the Hutchinson Cancer Research Centre in Seattle have found that blood vessels around pancreatic cancer tumours are compressed, forming a barrier which prevents effective drug delivery to the cancer cells. The researchers found that an enzyme called PEGPH20 expanded the blood vessels supplying the tumour by breaking down the fortified barrier compressing the blood vessels.

The surfaces of the blood vessels in pancreatic cancer contain an unusually large amount of a protective protein called hyaluronic acid, which acts as a barrier between the blood vessels and the cells they supply beneath. PEGPH20 breaks down the hyaluronic acid, reducing the surrounding pressure and expanding the diameter of the blood cells, which allows larger molecules, such as drugs, to pass through them.

When the UK researchers gave PEGPH20 to mice with the most common form of pancreatic cancer, pancreatic ductal adenocarcinoma, significantly more of the chemotherapeutic drug doxorubicin was taken up by the tumour. When PEGPH20 was used in combination with the chemotherapy drug gemcitabine, the average tumour size was reduced by approximately 50 per cent after 5 days, compared to a reduction of around 15 per cent when gemcitabine was used alone.

In similar studies in mice, the US research group showed that 83 per cent of tumours decreased in size after one cycle of treatment with the combination of PEGPH20 and gemcitabine - and 100 per cent of tumours decreased in size after three cycles. The group also reported a reduction in the amount of cancerous cells that spread to the lungs and liver. Both groups found the treatment with PEGPH20 and gemcitabine significantly prolonged the lifetime of the animals compared to just treatment with gemcitabine alone.

The UK’s study leader, Professor David Tuveson, said: “Adding this enzyme to treatments could be a game-changer for treatment of pancreatic cancer if clinical trials show it can be used to treat patients safely.

A trial to test the effect of PEGPH20-gemcitabine combination in pancreatic cancer patients is being carried out by Halozyme Therapeutics.

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