Does radiotherapy make aggressive childhood brain tumours resistant to further treatment?

The challenge

Diffuse midline gliomas (DMGs) are an incurable type of childhood brain cancer. Radiotherapy is the only treatment shown to prolong life in newly diagnosed patients, albeit briefly. Over the last three decades, many new therapies have been tested in DMGs either alongside or after standard radiotherapy, but none have yet improved survival. While radiation can effectively kill cancer cells, data from adult brain tumours suggest that the cells which survive exposure acquire new genetic changes, or mutations. Tumours with more of these mutations have worse outcomes.
 

The project

Dr Thomas Oliver, at University College London, has found similar patterns of mutations after radiotherapy in two childhood DMGs. Until now, it was thought the mutations which existed before treatment contributed to treatment failure. In this project, Dr Oliver wants to consider an alternative – what if radiotherapy is responsible for some of the mutations driving treatment resistance?

To test this, the research team will compare tumour samples from children who have and have not had radiotherapy. They will use cutting-edge sequencing technologies to identify mutations in cancer cells which would have been undetectable previously. From this project, they hope to provide a clearer answer on whether radiation is linked to the mutations that make DMG more aggressive. Their detailed data will also help them understand how tumours evolve after radiotherapy, and they hope that this might suggest which treatments will and won’t work for these cancers. 
 

The impact

If the researchers’ theory is correct, it could entirely change the approach to clinical trial design in DMGs. It would provide the basis for trialling new treatments before offering radiotherapy, instead of afterwards. If radiotherapy is shown to be limiting the success of treatments, these trials could deliver better outcomes for patients with this cancer. Even if this is not the case, this project will provide a much better understanding of how radiation changes DMGs, providing important information when identifying the best drugs to work alongside radiotherapy.