Trinity study discovers genetic mutation behind incurable childhood cancer

Scientists in Trinity College Dublin have discovered how a specific genetic mutation causes an incurable childhood cancer, and have successfully reversed its effects by slowing cancer cell growth in laboratory conditions.

The treatment for diffuse midline glioma (DMG) is so effective using drugs already used on other cancers that they have called for immediate clinical trials in humans with a view to developing a new drug targeting the disease.

Their work on the mutation, known as H3K27M, sets out how “a new understanding of the genetics of DMG progression indicates [that] a highly promising, therapeutic approach may be realisable, offering significant hope of improved treatments in the future”.

There are five to 10 DMG cases in Ireland every year; with eight already this year. Brain tumours of various types affect 45-50 children annually.

Covid-19: Outlook for coming four weeks ‘uncertain and dangerous’, says Nolan

---

Skin cancer ‘set to treble over 20 years’ with men at greater risk

---

Meath TD urges people to cover-up after skin cancer scare

---

Ex-High Court president Nicholas Kearns to step down from NMH board

---

The DMG findings were published in the scientific journal Nature Genetics on Thursday – the research is supported by Worldwide Cancer Research and the Brain Tumour Charity.

The scientists called for trials to begin on the already approved class of drugs called EZH2 inhibitors. These target the same key biological pathway involved in DMG, as they do successfully in lymphomas and sarcomas – two cancers common in adults.

"We've taken a huge step forward in our study of DMG tumours and hope that the insights will help us design and implement precision oncology-based treatment approaches in DMG patients in the future," said Prof Adrian Bracken of the TCD School of Genetics and Microbiology, who led the research.

Crucially, EZH2 inhibitors have already received approval from the United States Food and Drug Administration for the treatment of two types of adult cancer.

“We propose these drugs could be impactful for children with DMG and, as a result, call for clinical trials to begin next.”

The successful targeting of the DMG tumour was achieved on human neural stem cells.

“Ultimately, we hope that our work – together with that of others focused in this area – will lead to curative clinical approaches for what is a truly terrible disease that can devastate families and for which there are currently no therapeutic options,” Prof Bracken added.

Challenge to treat

Paediatric gliomas like DMG are among the most devastating of childhood cancers. Tumours typically arise in the brain and are very challenging to treat, with prognosis extremely poor.

“As such, effective therapeutic options are urgently needed,” he underlined.

Dr Jane Pears, paediatric consultant oncologist at Our Lady's Children's Hospital, Crumlin, who treats children with this disease, said these tumours were a devastating diagnosis for children and their families.

“The best treatment we can currently offer may extend survival for a few months but is not curative. We are now entering an exciting era of expansion of our knowledge of this disease at a molecular level which, in turn, will lead us towards more targeted treatments,” she said.

Through collaboration between researchers and doctors in clinical settings, “this will hopefully lead to the improved outcomes that we all so dearly wish to see”, she said.

Maeve Lowery, professor of translational cancer medicine at Trinity and academic director of Trinity St James's Cancer Institute, said: "This pivotal work illustrates the success of a precision oncology approach – where understanding how cancers develop on a genomic level can accelerate the development of more effective treatments with less side effects."

The research programme led by Prof Bracken would build on this success to continue to develop new and innovative treatment strategies for adult and childhood cancers, she predicted.

Dr Becky Birch, head of research at the Brain Tumour Charity, hoped this "really promising discovery" would pave the way for new and targeted treatments to be developed for children with DMGs.

“With average survival still heartbreakingly short at less than 12 months, we urgently need to find new options to help slow the growth of this rare and often-inoperable cancer and give children diagnosed more time to live.”