Canadian researchers hope new drugs possible for hardest-to-treat brain cancer

Findings of the study could help scientists around the world come up with new drugs

Canadian researchers have identified genes in brain cancer stem cells that fuel the growth and survival of glioblastoma in hopes their data will be mined to develop treatments targeting an aggressive tumour that claimed the life of Tragically Hip frontman Gord Downie.

The major challenge is that even after 99 per cent of a tumour is removed, a few remaining cells multiply like tentacles and regrow in another part of the brain where further surgery is no longer an option.

Dr. Peter Dirks, principal co-investigator of a study published Tuesday in the journal Cell Reports, said despite genomic research that has led to better drug therapies for various cancers over the last decade, there’s been little advancement in the treatment of glioblastoma, which has largely remained a mystery.

“It’s a miserable way to go because involving your brain it robs you of your identity,” said Dirks, who in 2003 discovered the existence of cancer stem cells in brain tumours and had a family member who died of glioblastoma.

“Having that happen a few years ago certainly has continued to reinforce my commitment to do the best that we can, to continue to try and push the needle forward,” said the neurosurgeon and senior scientist in brain tumour research at Toronto’s Hospital for Sick Children.

Findings of the study, which includes research by Dirks and investigators at the University of Toronto’s Leslie Dan faculty of pharmacy and the Cumming school of medicine at the University of Calgary, could help scientists around the world come up with new drugs beyond the mostly ineffective standard radiation and chemotherapy treatment, Dirks said.

His research team provided 10 patients’ glioblastoma stem cell cultures for an experiment using powerful genetic technology called CRISPR-Cas 9 to analyze all 20,000 genes from each of the patients’ samples to determine which are important for the proliferation and growth of glioblastoma cells.

Dr. Stephane Angers, co-principal investigator of that part of the study at the University of Toronto, said the protein Cas9 is akin to a homing device that targeted certain genes important for the progression of the tumour cells.

“It’s like you take all the components to make a car and put them on the sidewalk,” he said of the experiment that systematically analyzed each gene. “An engineer could tell you which pieces of the engine are important to make the car move forward. Our study basically was able to identify the pieces of the engine, which are the pieces within the cells that are really important to make the tumour cell grow.”

The technology could one day allow the “bad” genes to be cut out and disabled by Cas9, allowing disease-causing mutations in DNA to be replaced with new DNA sequences.

“There are about 400 genes that we found that are important for the growth and the life of these glioblastoma tumour cells and of these we need to hone in on a subset that are candidates for a new drug, and I would say 20 to 30 of them for sure,” Angers said.

“We and others are now going to try and develop inhibitors, drugs, small molecules, antibodies to interrupt the function of these genes. What we’re now providing the scientific community is the blue book, if you will, the instruction manual, of how our glioblastoma cancer cells are wired and what is important in their circuits for driving the growth programs.”

Among the thousands of genes analyzed was one called DOT1L, which was found to be necessary for tumour persistence in seven of the 10 patients’ cultures.

Dr. Samuel Weiss, at the Calgary medical school, was part of the collaboration that demonstrated the same gene is also involved in the growth of some leukemias, for which a particular drug is currently being used as a treatment.

Angers said that drug does not enter the brain well so it could not immediately be tested in glioblastoma patients though it could potentially be modified to improve its delivery to the brain and be investigated through clinical trials to determine if it would be beneficial.

Both Dirks and Angers said that while their study may point to tailored treatment in the future, they cautioned much more research remains to done to put the pieces of the glioblastoma puzzle together as researchers grapple with the disease that also took the life of New Democrat MP Paul Dewer as well as American senators John McCain and Ted Kennedy, and former vice-president Joe Biden’s son Beau Biden.

The survival rate is about eight per cent over five years for the disease that every year is diagnosed in about 1,500 Canadian adults and 150 children. The average period of survival following diagnosis is about 14 months.

Camille Bains, The Canadian Press

Like us on Facebook and follow us on Twitter.

Just Posted

Mounties identify woman found dead on Kelowna beach

“Our investigators do not believe criminality was involved.”

Pacific Poke bowl lovers can get a free taste at the restaurant’s ‘Grand Opening Event’

The restaurant will offer some of its specials Thursday evening at its Kelowna location

Youth Shelter Fundraiser encourages kids to play for a good cause

The fundraiser takes place April 27 at the EnergyPlex

Tribute to Kelowna’s Chinese Canadian pioneers planned

A tribute to Kelowna’s historic Chinese Canadian community got underway this weekend.

Update: RCMP confirm body found at Kelowna’s Gyro Beach

Police tape is blocking part of the beach and several RCMP officers are on scene.

Homeless activists outside Notre Dame demand ‘a roof too’

Wealthy people have donated millions to effort to rebuild cathedral after devastating fire

B.C. VIEWS: NDP’s lawyer show is turning into a horror movie

Court actions pile up over pipelines, car insurance, care aides

South Okanagan community bands together on social media after shootings

Many in Penticton have turned to social media to express their condolences

PHOTOS: Green Party Leader Elizabeth May says ‘I do’ on Earth Day

May and John Kidder got married Monday morning in Victoria

Okanagan resort seeking connnection to rail trail

Predator Ridge Resort slated to present wish for trail from resort to ORT to Vernon council

South Okanagan society looking to bring new racing event to their park

The Desert Park Exhibition Society board is looking into hosting another major event

Okanagan power outage scuttles – but not ruins – city’s mission’s Easter meals

Vernon’s Upper Room Mission will serve Easter dinner a day later due to downtown power outage

Waterway Houseboats wins $2 million for damages caused in 2012 flood

Houseboat company wins lawsuit involving Province of British Columbia, District of Sicamous

Sri Lanka invokes war-time military powers after nearly 300 killed in Easter bombings

Sri Lanka’s minister of tourism says 39 foreign tourists were killed in the Easter Sunday attacks

Most Read