Combining drugs ‘may extend lives of children with incurable brain cancer'
Combining two powerful drugs could extend the lives of children with incurable brain cancer, experts believe.
Two existing treatments for leukaemia and melanoma cancer were found in the lab to slow the growth of DIPG (diffuse intrinsic pontine glioma) brain tumours.
Scientists will carry out further work before testing the combination in a clinical trial on children but they hope the therapy could be put into practice soon.
DIPG tumours develop in the brain stem and are highly aggressive, mainly affecting children aged five to 10.
There is no cure and most children die within 18 months of diagnosis.
The disease is rare, affecting around 20 to 30 children each year in the UK.
In the new study, scientists from the Institute of Cancer Research (ICR), London, found that the combination of two existing drugs was effective against cells that had evolved resistance to a single drug treatment.
The drugs are called MEK inhibitors, which often work well against tumours before the cancer becomes resistant to the treatment.
Researchers evaluated an MEK inhibitor called trametinib in mice, and found that on its own it had little effect.
Further work found that the enzymes MEK 1 or MEK 2 were involved in allowing the resistance to happen.
The researchers then tried using a drug, dasatinib, that could inhibit these enzymes alongside trametinib to treat DIPG cells taken from mice.
They found that the combination of the two drugs, each with a different mechanism of action, slowed down tumour growth in cells, which had been resistant to trametinib when it was used on its own.
The combination managed to cut growth in cancer cells grown on mouse brain tissue by over 60%.
Chris Jones, professor of paediatric brain tumour biology at the ICR, said: “We’ve grown up tumour samples from children with brain cancer in the lab to really understand the biology of their disease.
“We now have a much better understanding of the ways that DIPG brain tumours can mutate, and how they can evolve resistance to treatment with a single drug.
“It has allowed us to identify what we hope could become a successful new combination treatment for this terrible disease.
“Our findings will need to be validated further in the lab, but, because we are using existing approved drugs that we know are safe, we hope it won’t be too long before the new treatment enters clinical trials.
“These promising results have emboldened us to keep analysing patient samples and modelling their treatment response, because it shows how specific some of the treatments are that we’re needing to develop.
“We hope to identify further new combinations that can benefit children with DIPG tumours that carry other DNA mutations.”
Professor Kristian Helin, chief executive of the institute, said: “Cancer’s ability to evolve to become resistant to treatment is one of the biggest challenges we face in creating effective targeted cancer therapies.
“But if we can identify the mechanisms of resistance, as in this study, we can stay one step ahead of cancer by proposing new treatments or drug combinations that can keep patients alive and healthy for much longer.
“It’s vital that we can continue to identify ways to overcome cancer’s ability to adapt and evolve in children’s cancers such as DIPG – so we can bring forward new treatments for young cancer patients who so desperately need them.”
– The study, published in the journal Cancer Discovery, was funded by a range of cancer charities, including Christopher’s Smile, Abbie’s Army, Islastones Foundation, the CRIS Cancer Foundation, Cancer Research UK, Children with Cancer UK and the Ollie Young Foundation.