Creating advanced models to test new treatments for malignant rhabdoid tumours

The challenge

Malignant rhabdoid tumours (MRT) are rare but aggressive tumours that occur in very young children. It is very hard to treat, with less than 40% of patients surviving overall.  Despite this , few new drugs have been introduced as more evidence is needed. In short, there is currently very little to offer the many children with MRT whose treatment fails. New treatments are urgently needed, but researchers also need better ways to research these treatments.

Scientists usually use patient-derived xenografts (PDXs) to study MRT. These are mice that have been implanted with tumours from real patients.  However, these models have limitations— the tumours aren’t always implanted in the same place as the original patient’s tumour, they do not always allow for live imaging to track how the tumour grows, and they do not always reflect the full diversity of disease seen in patients. In addition, researchers do not always use the same set of models, which makes it hard to compare drug testing results. 
 

The project

Dr Daniel Williamson aims to build a set of models specially designed to better predict which drugs should be effective for children with MRT. He has assembled an expert team of investigators at Newcastle University, which includes Dr Rebecca Hill and Professor Gareth Veal.  Together, they will create and evaluate their new models alongside a large collection of existing MRT models to ensure that the best option is used for future research. 

Once they have identified the best models, the researchers will use them to test new treatments for MRT. MRT is caused by the loss of a single gene, called SMARCB1. Reactivating this gene in MRT cells can make them stop growing excessively and behave like normal non-tumour cells. Dr Williamson’s team will test promising medicines that mimic the behaviour of SMARCB1 to see how they work and whether they could be used to improve existing treatments. 

The impact

The researchers’ findings could be integrated into ongoing international clinical trials which investigate MRT in the brain (for example SIOPe ATRT01) to bring results to patients as soon as possible. The researchers also plan to share their findings and models so that future scientists can test and compare drugs which might benefit children with MRT. Creating a standardised testing system for new drugs and identifying potential treatment targets will help develop better treatment options for patients.