Researchers in Canada have discovered why a group of childhood brain cancers are resistant to radiation therapy in a study using mice. 

Radiation therapy, the only treatment available for medulloblastoma — the most common malignant brain tumour in children — is initially effective but often loses its potency when the tumours recur, especially in the most aggressive cancers.  

Researchers at the Hospital for Sick Children and EARA member University of Toronto used a technique called CRISPR-Cas9 gene editing on these tumours to find the ones that are responsible for the resistance to radiation therapy.  

By exposing the gene-edited tumour cells to radiation, the researchers found that the absence of a single tumour-suppressor gene, called TP53, made the cells resistant to radiation. This discovery confirms clinical observations that children with most aggressive tumours have mutations in the same gene.  

The researchers also found three genes, involved in the repair of DNA, that did the opposite and made the cells sensitive to radiation. Using mice with tumours derived from patients, the researchers treated the mice with Peposertib — a drug which targets one of these three genes and is currently being tested in several clinical trials for adult cancers — and found that this treatment made the tumours susceptible to radiation treatment.    

“These high-risk tumours still have vulnerabilities and if we can identify those vulnerabilities, we can potentially find therapies that we could bring to the clinic,” said Alexandria DeCarlo, first author of the study. 

These findings, published in Cell Reports Medicine, could contribute to improving the standard-of-care for brain cancers, enabling children to live longer and better lives.