‘Bar coding’ cells to track development of brain cancer
Canadian-led research team hopes to improve treatment of aggressive glioblastoma
A Canadian-led international research team is using a “bar-coding” system to investigate the growth patterns of individual cells that make up the deadliest form of brain cancer, with the hopes of improving treatment.
Known as a glioblastoma, it’s considered among the “nastiest” of human cancers and is the type of brain tumour diagnosed last year in Tragically Hip frontman Gord Downie.
Each year in Canada, about 1,500 adults and 150 children are diagnosed with a glioblastoma, an aggressive tumour notorious for its complex genetic makeup and poor response to treatment.
Glioblastoma has an average fiveyear survival rate of only about10 per cent, and most people succumb to the disease within roughly15 months of diagnosis.
But research led by the Hospital for Sick Children in Toronto and the University of Cambridge in the U.K. is taking a novel approach to better understanding how individual cells in the tumour contribute to its growth and what types of drugs might best target this highly invasive brain cancer.
“What we did here was we took human tumours, broke them up into individual cells and then we infected those with a short DNA sequence,” said co-principal investigator Dr. Peter Dirks, a neurosurgeon and researcher at Sick Kids.
In the lab, every cell was tagged with a different DNA bar code, giving them a unique identifying marker, Dirks explained.
“That gets integrated into the DNA of that cell and, as that cell divides, all the daughter cells of that labelled cell share the same bar code. It’s a very powerful way of just tracing the potential of each cell in the tumour.”
These human glioblastoma cells were then put into the brains of specially bred lab mice and allowed to continue dividing to form tumours. When the tumours were removed, DNA from each cell was sequenced and their bar codes identified.
“What that sequencing was able to do was tell us what are the bar codes that are there,” said Dirks.
Using this cell-tracking strategy, the researchers found that only a small proportion of the bar-coded cells could give rise to long-term tumour growth, suggesting that a large proportion of patient tumours contain cells that cannot multiply to make tumours grow.
They found that glioblastoma is made up of many different clones — mini-cancers comprising clumps of genetically identical cells within the tumour — and most followed a growth pattern consistent with the stem cell model of cancer, in which a minority of stem cells are responsible for tumour growth.
What’s key about these findings, published Wednesday in the journal Nature, is they suggest a different way of targeting the brain tumour.
“It gives me hope that, with this disease, we’re not going to need 20 different drugs to treat it. Maybe we’ll just need several that target the specific behaviour of these cancers.”