A new study has found that currently incurable childhood brain tumours can be split into ten different diseases, each of which requires specific treatment.
This is significant because a personalised approach is likely to be more effective than lumping them all together – and many types have mutations which can be targeted by existing treatments approved for adult cancers.
While these ‘high grade’ tumours are rare, survival rates in those under 19 years of age are extremely poor – sufferers are only expected to live an average of 9-15 months.
The study, published in Cancer Cell, comes from the Institute of Cancer Research in London, and examined genetic data from children or young adults up to the age of 30 with high grade glioblastoma or diffuse intrinsic pontine glioma (DIPG).
Looking at the data - from 910 cases in 20 previously-published analyses and 157 new cases – researchers found the tumours could be divided according to factors such as age at diagnosis, area of the brain, number of genetic mutations and errors in key genes that drive the disease.
The latter point is vital, since the study found that while some were driven by a single genetic error in which two genes were fused together, others had tens of thousands of genetic errors.
“Treating cancer based only on what we see down the microscope simply isn’t good enough anymore,” said study leader Professor Chris Jones, Professor of Childhood Brain Tumour Biology at ICR.
“We need to start thinking about these as completely different cancers and diagnosing and treating them based on their genetic faults. It’s exciting that several types look like they could be clearly treatable using either existing drugs on the market or other treatments under development,” he added.
Tumours with mutations in the BRAF gene were much less aggressive than some others, and could be treated with adult cancer drugs that target BRAF mutations, the research suggests.
The ICR study found mutations in common cancer genes such as PDGFRA, KIT, MYCN, EGFR, CDK6 which can also be targeted by existing therapies.
Pharma companies will be interested in the new potential therapeutic targets which the research unearthed in each subtype. These include the gene TOP3A, which is involved in DNA replication, in tumours with a specific type of histone mutation called H3.3K27M.
In a statement, ICR said: “Three of the subtypes were distinguished by the presence or absence of different mutations in genes that produce histones – proteins that DNA is wrapped around to pack it tightly into cells. Histones are also involved in turning off and on certain genes – a role that can be very important in cancer.”
While no existing drugs target histone mutations, their presence in these subtypes could point the way to new areas of drug development and treatment.
The research was funded by the ICR and various charities: Cancer Research UK, CRIS Cancer Foundation, Abbie’s Army, The Lyla Nsouli Foundation, Christopher’s Smile and the INSTINCT network funded by The Brain Tumour Charity, Great Ormond Street Hospital Children’s Charity and Children with Cancer UK.