Groundbreaking research in epigenetics has led to the development of a potentially life-changing treatment for children with brain cancer. Now in its pre-clinical phase, the research shows that epigenetic drugs are as therapeutically effective as conventional chemotherapy, but not as toxic, meaning it would have fewer side effects in the patient.
High mortality rates for children with brain cancer highlights need for new therapies
Paediatric brain cancers are the second leading cause of death in children. Due to the aggressive nature of these cancers, the five-year survival rate is less than one per cent.
Research shows that the biological and molecular makeup of brain tumours in children are unique and cannot be directly compared to those in adults. Treatments designed for adults therefore don’t work as effectively in children and can often cause long-term health problems.
“Chemotherapy can affect the growing cells in children,” explains research lead Dr Rasika Samarasinghe. “The high levels of toxicity impact their growing minds and bodies, and have long-term effects on their physical growth and mental capacity.”
With little funding and attention directed towards paediatric brain cancers treatments, the survival rates for children haven’t changed for the past 30 years.
Epigenetics drugs found to have fewer side effects compared to conventional chemotherapy
Six years ago, a groundbreaking Deakin study found that certain epigenetic drugs, such as histone deacetylase (HDAC) inhibitors, are a usable and effective therapy for paediatric brain cancers and could improve the quality of life of children receiving treatment.
The initial research, which focussed on two aggressive forms of childhood cancers – malignant rhabdoid tumour (MRT) and atypical teratoid rhabdoid tumours (ATRT) – used pre-clinical cell culture and animal models to show that the use of continuous low-dose Panobinostat treatment was able to stop cancer progression and induce cell death.
Panobinostat is a HDAC inhibitor that works by reactivating tumour suppressor genes which are usually silenced in cancers.
Analysing epigenetic changes serves as diagnostic tool for more effective treatments
Building on the research from the critical Deakin study, Dr Samarasinghe and her team have commenced pre-clinical studies analysing epigenetic changes in paediatric brain cancers to show unique drug targetable pathways that could offer hope for better outcomes in children with the disease.
“The benefit of drug repurposing is that you skip the five-to- six-year phase of testing these drugs for toxicity,” explains Dr Samarasinghe. “These drugs we are researching have already been tested on other disorders, so we’ve shortened that phase, and have been able to create a bank of drugs that could be used to tailor treatments to individual patients based on their epigenetic and molecular markers.”
Dr Samarasinghe says the preclinical studies could translate quickly into the clinical phase. One part of the study involved looking at epigenetic changes of a cohort of patients with an aggressive form of brain cancer known as Glioblastoma, analysing the changes in the epigenomic aspect, and then using these changes to find genes that could be targeted using specific drugs.
“We tested a range of drugs to see if they have an effect on the cancer cell lines,” she explains. “All these cell lines have the genetic profile of the cancer and after treating these cells with these drugs, we were able to narrow it down to a couple of drugs that had a better effect on the cancer cells than the current chemotherapy given to children. Interestingly, these drugs were again HDAC inhibitors.”
By using drug repurposing techniques and innovative cell culture techniques, the research has been able to find treatments that show significant toxic effects on cancer cells but not on non-cancerous cells.
“We hope to now test these novel drugs in animal models,” Dr Samarasinghe said. “Through our collaborations we will test the therapeutic effects of the HDAC inhibitors in zebrafish and mouse models. And if that all looks good, we could move on to Phase 1/2 clinical trial.”
Research shows epigenetic advancements are shaping the future of personalised healthcare
Beyond cancer care, this research has inspired the development of other epigenetic therapies and diagnostics for mental health and degenerative disorders, paving the way for increased focus on precision medicine. By tailoring treatments to individual patients based on genetic and molecular markers, epigenetic advancements are shaping the future of personalised healthcare.
“We’re always looking for personalised treatments. Everyone’s genome is different, and we have to keep that in mind – that treatments need to be different, especially for children.”
