NCRI Cancer Conference 2009: Aurora, BRCA and unstable chromosomes

With just 24 hours’ notice, Professor Ashok Venkitaraman stepped in at the NCRI conference to deliver an enlightening talk on how chromosomes become unstable in cancer, after the planned speaker had to cancel at the last moment.

Professor Venkitaraman’s specialist field is ‘chromosome instability’ – the way the cell’s genetic information becomes more and more garbled in the development and progression of cancer.

His goals are to understand exactly how chromosomal instability can drive the development of cancer, and to translate this knowledge into advances in cancer diagnosis and treatment.

Insights from BRCA2

Professor Venkitaraman has focused a large part of his research on the BRCA2 gene. People who carry inherited faults in this gene have a high chance of developing breast and ovarian cancer at some point in their lives. Studying exactly why this happens has lead to insights that are applicable to a wide range of cancers.

As Professor Venkitaraman puts it, “We can learn a lot about the genetic drivers of cancer by studying genes that we know are involved in familial cancers.”

The protein produced from the BRCA2 gene teams up with our cells’ molecular ‘repair kits’ to patch up breaks in our DNA that occur during everyday life. But without a working copy of BRCA2, our cells can’t repair this damage properly.

And that’s not all – more recently Professor Venkitaraman has found that BRCA2 is needed for a cell to divide into two daughter cells. As he explained, most cells that lose BRCA2 activity will usually die. But occasionally, these damaged cells are able to continue to survive in certain tissues like the breast and ovaries – as they grow and divide, their genetic material becomes more and more damaged and, over time, this can lead to cancer.

The Aurora story

The second part of his talk focused on the fascinating story of Aurora-A, a protein that is present in unusually high levels in about a third to a half of common cancers.

Under normal circumstances Aurora-A is an integral part of a system of ‘checkpoints’ that ensures that cells only divide at exactly the right time.

But Professor Venkitaraman believes that if the levels of Aurora-A get too high, this can over-ride one of these ‘checkpoints’ and force cells to divide when they’re not ready to. This can lead to chromosomal instability and may contribute to the onset of cancer.

Interestingly, many drugs including taxanes, like paclitaxel, target cancer cells at this particular checkpoint and there’s now evidence that high levels of Aurora-A can cause resistance to these drugs. This latest discovery is now being used to try to improve cancer treatments, with the launch of a new trial to find out whether blocking Aurora-A with an inhibitor drug can overcome resistance to taxane treatment.

Professor Venkitaraman’s team is also looking for other proteins that are involved in this cell cycle ‘checkpoint’ in cancer – these could act as good markers for predicting how patients will respond to today’s taxane treatments, as well as pointing to new treatments for the future.

Helen

Helen George is Cancer Research UK’s Head of Science Information