Tumour evolution in brain cancer

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Published: 11 May 2018
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Dr Roel Verhaak - The Jackson Laboratory, Farmington, USA

Dr Verhaak talks to ecancer at the Cancer Research UK Brain Tumour Conference 2018 in London about tumour evolution in brain cancer and the process where a primary tumour evolves to become a more aggressive tumour and becomes a recurrent cancer.

He goes on to discuss the issues in treating and conducting research into this field.

I spoke about tumour evolution, the process where a primary tumour evolves to become a more aggressive tumour and becomes a recurrent cancer. It’s a complex process but essentially think of a cancer as millions of cells; when you treat that cancer with chemotherapy and radiation a lot of those cells will die but the few cells that survive that process are the ones that are more resistant to that treatment and they then fuel the tumour progression.

Why is this so important to look at?

Because if you want to make treatments more effective you need to go after that population of cells that is more resistant at the start. By also trying to attack those cells you might make treatments more effective and give better outcomes to patients.

What have you found so far?

What have we found so far? That it’s a very difficult problem, first of all, but we have increasingly comprehensive technologies in order to be able to study that process. So it starts with the technology. The second part that we need is the right tissue specimens from those cancers and it has also been quite complicated to get those tissues for all kinds of practical and logistic reasons. So we’ve created a network of collaborators in order to get to the number of tissues that we need in order to be able to perform these studies with sufficient statistical power. We’ve made a start, we’ve made an in-way into doing the actual studies.

It’s a little early to say what we’ve found so far. It’s a bit of a no-brainer but it’s complex, that’s what we found. But I also believe that once we are able to finish up our full study, and we hope to get to 1,500 patients in our full study, I think that we will be able to make conclusions that are statistically robust and that it’s just too early now to really find those.

What would be the next step in translating this research into the clinic?

The next step of that would be if we see, for example, a pathway that is enriched after recurrence that might suggest that that pathway plays a particular role in defeating the treatment, if you will. Then you could start to think of preclinical research where you find treatments for that specific pathway and if those are successful preclinically then you can start about rolling those out clinically – via phase I and II and III trials.

Maybe I should also mention that we recently found that extrachromosomal material may play important roles in fuelling that tumour evolution process. So these are small circular DNA elements that only exist in cancer cells and that cause activation and amplification of oncogenes. We believe that those are actually key in this whole process.