Brain cancer could be triggered by the healing process from a brain injury, new research has said, in findings which could yield new breakthroughs in patient therapies.
The tumours of 26 patients with glioblastoma were analysed in the Canadian research project, and found that mutations can affect the process of new cells being created, which can therefore stimulate tumour growth.
“Our data suggests that the right mutational change in particular cells in the brain could be modified by injury to give rise to a tumour,’ says report author and neurosurgeon Peter Dirks, from The Hospital for Sick Children in Toronto.
“Glioblastoma can be thought of as a wound that never stops healing.
“We’re excited about what this tells us about how cancer originates and grows and it opens up entirely new ideas about treatment by focusing on the injury and inflammation response.”
In the study, published in Nature Cancer, researchers used single-cell RNA sequencing and machine learning technologies to map out the molecular make-up of glioblastoma stem cells.
The team found new subpopulations of glioblastoma stem cells which bear the molecular hallmarks of inflammation and are comingled with other cancer stem cells inside patients’ tumours.
These findings, Dr Dirks said, suggest that some glioblastomas start to form when the normal tissue healing process — which is supposed to generate new cells to replace those lost to injury — is interrupted by mutations.
The mutant cells will then continue to multiply, spurring tumour growth, although it may be many years before a patient becomes symptomatic.
In the research, cells from the tumours of 26 patients were collected, and in total almost 70,000 were analysed using single cell RNA sequencing.
The team found evidence of ‘extensive disease heterogeneity’ and that each tumour contained multiple subpopulations of molecularly-distinct cancer stem cells.
This will, therefore, make cancer recurrence more likely, as existing therapies are unable to wipe out all the different ‘subclones’.
However, as a result of this understanding, new therapies and bespoke approaches could be developed.
“We’re now looking for drugs that are effective on different points of this gradient,” adds co-author and cancer genomicist Trevor Pugh, from Princess Margaret Cancer Centre in Toronto.
“There’s a real opportunity here for precision medicine — to dissect patients’ tumours at the single cell level and design a drug cocktail that can take out more than one cancer stem cell subclone at the same time.”
