Spotting New Markers of Cancer

University of Otago researchers are delving into the molecular mechanisms involved in the development of cancer as a way of taking research from the laboratory bench to the clinical setting.

While some scientists are studying possible new drug therapies at one end of the scale, and others are focused on cancer genetics at the other end, the group at the Dunedin School of Medicine’s Department of Pathology is looking to bridge that gap.

In the process the group, involving Professor Antony Braithwaite, Professor Michael Eccles and Dr Janice Royds, in collaboration with Professor Bruce Baguley at the University of Auckland, has identified a number of markers and potential therapeutic targets for breast cancers, brain tumours and melanoma.

Professor Braithwaite is focusing on the gene P53, a well-known tumour suppressor gene. “That gene is more often defective in tumours than any other single gene that has been identified,” he says.

Of particular interest is how other proteins alter the way P53 functions, especially the protein YB1.

“It’s been known for a while that this protein, which largely sits dormant in the cytoplasm, only becomes active when it goes to the nucleus. What we’ve discovered is that P53 makes it go to the nucleus, and when it gets to the nucleus it partially disables P53. That predisposes cells to become cancerous,” he says.

“There is now evidence to support the idea that YB1 is a potential new therapeutic target.”

Professor Braithwaite has also shown that nuclear YB1 shows up in precancerous breast cells making it a useful marker in diagnosis.

PAX family of genes

Meanwhile, Professor Michael Eccles has been studying genes which are switched on during foetal development and then switched off again before adulthood. What has been found is that some of these genes get turned back on again in some cancers.

Of particular interest has been the PAX family of genes which has been implicated in melanomas and brain cancers. Once again these genes may be useful as diagnostic markers and as new therapeutic markers.

The third part of the programme revolves around the work of researcher Dr Janice Royds who has been studying brain tumours with the same goals of identifying markers and possible therapeutic targets.

She has been focusing on tumours of the glial cells. They come in two forms, gliomas and a particularly nasty form called glioblastomas.

“If you do a patient cohort analysis you find that the glioblastomas often fall into one of two groups: ones that allow patients to survive only a few months and ones that see the patients survive for a few years after diagnosis,” Professor Braithwaite says. “Pathologists have no way of distinguishing between the two.”

Dr Royds has been studying these tumours and has identified a marker that distinguishes between them.

“We believe it is a reliable marker and hope that it will be translated into the clinic in the very near future,” he says. “Also, if we can understand more about how this marker works then we might be able to develop another therapeutic.”

From lab to clinic

Professor Braithwaite says that their programme underlines the usefulness of studying basic cell biology and developmental biology to try and identify a cancer marker or a potential therapeutic target.

“What we’ve tried to do is shift our basic science to the clinic and that’s actually turned out to be quite useful. For example, in the project on YB1 it has allowed us to ask what are we doing at the bench that helps us to understand some of the properties of these tumours,” he says.

“You need to know what a tumour is like. You need to ask questions of clinicians to understand the problem but you can use your cell biology to develop new tools and new ways of approaching the development of biological markers and therapeutics.”

Professor Braithwaite says there is very good evidence worldwide that if a tumour is diagnosed early, the chances of five or ten-year survival are better than 90 percent.

“If a tumour is diagnosed late, usually when it has spread a bit, the five-year survival rate is very low, less than 20 percent. And that has not changed since the 1970s,” he says.

“For me, markers are more important than therapies. If you can diagnose a cancer really early, before it spreads, surgeons will do the rest.”

This research is funded by the Health Research Council of New Zealand.

To find out more

www.hrc.govt.nz