Wednesday, August 14, 2013

Sydney team develop new cancer drug

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A new class of cancer drug

Images reveal a neuroblastoma cancer cell before and after treatment with a new class of cancer drugs. No audio.

Sydney researchers have developed a new class of cancer drugs, the first to target the internal structure of tumour cells.

The new drugs, which have been trialled in rodents, destroy one of the fundamental building blocks of cancer cells - the molecules that form the struts and cables of their interior scaffold.

Tests in cell cultures show the drugs, the culmination of 30 years of research, are effective against every cancer type tested, including difficult-to-treat childhood cancers such as neuroblastomas.

Neuroblastoma cancer cell.

Green for danger: A neuroblastoma cancer cell before treatment. The new class of drugs destroys molecules that form the internal struts or cables (represented here by the green lines) that hold a cancer cell together. Photo: Howard Vindin

"Our drug causes the structure of the cancer cell to collapse - and it happens relatively quickly,'' said lead researcher Peter Gunning of the University of NSW. "It is much like what happens when you see a building collapse on the TV news.''

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Professor Gunning hopes the drugs, called anti-tropomyosins, will soon be added to the few other chemotherapy drug classes. ''This is a long sought-after big target.''

Scientists have tried to attack the architecture of cancer cells for decades, but until now they had been unable to develop a drug that would only destroy tumour cells and not other tissues in the body.

Neuroblastoma cancer cell.

Downsized: A neuroblastoma cancer cell after treatment. Photo: Howard Vindin

''Nobody has ever made a drug like these,'' he said.

The new drugs target a protein called tropomyosin, a molecule that pairs with another protein called actin to organise the internal structure of all cells in the body including cancer cells.

The protein pairs also form the smallest contracting units inside muscles such as the heart.

Most other research groups have focused on finding drugs that worked against actin. The problem with targeting this protein is that the actin found in the heart and other muscles is almost identical to the actin found in cancer cells.

''The issue [with those drugs] is the heart stops beating,'' he said.

When Professor Gunning and others discovered that tropomyosin in heart and other muscle cells was different to the tropomyosin in cancer cells, they saw a way around the problem. His group developed a computer model of tropomyosin and screened thousands of potential pharmaceutical targets for an appropriate drug candidate.

Out of 25,000 targets, most simple molecules, only one killed tumour cells in the lab.

When the group refined its computer models they identified another five drugs that are now being tested in animals in the US to establish which molecule will be trialled as a chemotherapy treatment in humans.

''The aim is to be able to initiate a trial for neuroblastoma at the end of 2014,'' said Professor Gunning, whose findings are published in journal Cancer Research


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