Australian researchers have determined the three dimensional structure of an important protein detected on cancer cells, paving the way for the development of new drugs to treat cancer.

The protein – the epidermal growth factor receptor – was first discovered 20 years ago. Ever since, laboratories all over the world have tried to understand how it works. In 1997, a group of Melbourne scientists joined forces to also tackle the problem. Now their efforts have paid off, with a discovery that is challenging the current view of cell signalling.

"We’ve discovered how the receptor recognises the protein and transmits the signal to cancer cells to grow," said Professor Tony Burgess at the Ludwig Institute for Cancer Research. "If we can turn this off, the cells will stop growing."

Professor Burgess’s colleagues include scientists at CSIRO Health Sciences and Nutrition and The Walter and Eliza Hall Institute of Medical Research. All are members of the Collaborative Research Centre for Cellular Growth Factors, and their findings are published in the current issue of the international journal Cell.

The EGF receptor works like a 'lock and key' system, where the protein must fit the receptor exactly. But it is the second step of this process – the 'turning of the key' – the researchers are trying to halt.

"We want to stop the lock turning,” explained Professor Burgess.

This means developing a new class of anti-cancer drugs based on rational drug design, to act as inhibitors.

In contrast, most current drugs to treat cancer have been developed on a wing and a prayer. "You take a poison and hope it will kill the cancer before it kills the patient," said Professor Burgess.

Late stage cancer patients stand to benefit initially . "Every late stage brain tumour has some EGF receptors on the surface," said Professor Burgess. "So we think they might be very good targets for our drugs."

A soluble form of the binding drug has been developed and is on schedule to be trialled in patients in 2004.

In the meantime, the researchers are using a computer to search big chemical libraries for structures that will bind to the EGF receptor. Once they find these, they will test them in animals. "We’re only two to three years away from helping patients," predicted Professor Burgess.

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