New insight into how childhood brain tumours develop

A recent study gives vital insight into childhood brain tumours

We’ve funded many of the world’s most successful trials of new treatment for children with cancer, and this has contributed to childhood cancer survival rates rising to an all-time high.

But childhood brain tumours remain an area where progress has been slow. We still need to increase our understanding of the fundamental biology that causes brain tumours – only then will we be able to develop more effective treatments in the future.

Thankfully, knowledge in this area is increasing in leaps and bounds, as illustrated by a study published a few weeks ago in the journal Cancer Cell, in which Cancer Research UK scientists played a role.

The study gives us vital insights into how brain tumours develop in children and how we can find better treatments for this devastating type of cancer.

What did the researchers do?

The researchers looked at the role of a gene called MYCN in different types of brain tumours. MYCN is essential for normal cell growth but has the potential to cause cancer when it becomes damaged. It’s frequently involved in a range of cancer types, including brain tumours.

Working in a mouse model of the disease, they studied immature cells, known as stem cells, from three different parts of the brain and at different stages during development – both before and after birth.

They tested whether engineering the stem cells to contain an extra copy of the MYCN gene would cause a brain tumour to form. They also looked at whether these tumours would then respond differently to treatment.

What did they find?

They found that tumours developed when the MYCN gene was added and – crucially – that the tumours looked and behaved differently depending on which part of the brain they came from, and at what point in time they arose. The tumours also had different characteristics that identified which part of the brain they had come from.

Crucially, these tumours responded differently to treatments, depending on where and when they originated – even though they’d all arisen from stem cells containing an extra MYCN gene.

For example, tumours arising before birth, in a part of the brain called the cerebellum, responded to a drug called cyclopamine, whereas tumours arising after birth did not.

What does this mean?

This is a new and exciting development that could have consequences for how children are treated in the future. But the results need to be confirmed in further studies.

Previous research has already shown that abnormal activity of certain genes such as MYCN can contribute to the development of childhood brain tumours. But this work shows that we also need to consider when the tumours arose – before or after birth, and where in the brain the tumour originated. These two factors affect what a tumour looks like, how it behaves and how it is likely to respond to treatment.

How have our scientists been involved?

The research was primarily a collaboration between US and Swedish researchers, but also involved Dr Louis Chesler, a Cancer Research UK-funded researcher based at The Institute of Cancer Research who’s worked on MYCN for some time.

We spoke to Dr Chesler about his involvement in the work, and where he sees the field developing next.

Dr Chesler developed the mouse model that formed the foundation for this research. Cells from this model were stimulated with MYCN to see if tumours would arise. The resulting tumours were then isolated and studied to discover their characteristics and where they originated from.

What next?

Some of the drugs used in this study are already being tested in the clinic. But according to Dr Chesler, we need to study the role of MYCN further to fully understand how it can be used as a target for new treatments.

This research has exciting implications for future treatments and Dr Chesler says “we hope that within the next two years we will have a drug that can target MYCN directly”.

Reference

Swartling, F. J. et al. (2012). Distinct Neural Stem Cell Populations Give Rise to Disparate Brain Tumors in Response to N-MYC. Cancer cell, 21 (5), 601-13 PMID: 22624711