Ontario and B.C. researchers, working in unusually close collaboration, have led 140 scientists in 46 cancer labs around the world to analyze material from the frozen, pre-served brain tumours of 1,000 children to map out the genes of medulloblastoma brain tumours, the leading cause of pediatric cancer deaths.
Their work on the molecular makeup of the tumours, published Wednesday in the journal Nature, paves the way for development of new, less toxic and more effective therapies.
Existing treatment involves surgery to remove as much of the tumour as possible, brain and spinal cord radiation, aggressive chemotherapy and bone marrow transplants.
Five-year survival rates range between 60 and 70 per cent, but survivors are left with severe side effects from treatment, including intellectual and physical impairments, plus a higher risk of secondary cancers.
While the study helped define the molecular makeup of medulloblastomas, the team of researchers, co-led by B.C.’s Marco Marra, made a completely unexpected finding about a possible genetic link between Parkinson’s disease and one of the four brain cancer subtypes. In Parkinson’s, a particular gene is underactive and plays a role in brain cell death; in the most common subtype of medulloblastoma, however, it is duplicated, or overactive.
“So it appears to have the opposite effect in brain tumours,” said Marra, director of the BC Cancer Agency’s Michael Smith Genome Sciences Centre.
“Dialed back, you get one disease and dialed up another,” he added. “That doesn’t prove a linkage but it’s pretty compelling.”
Marra noted the finding may prompt research into whether drugs designed to suppress the gene will kill off brain tumours.
Marra’s co – leader, Dr. Michael Taylor, said despite research that has shown medulloblastoma is actually four different diseases, the tumours are largely still treated all the same and the collateral damage is harsh and extensive.
Taylor, a pediatric neurosurgeon and scientist at Toronto’s Hospital for Sick Children, said current treatment methods are so aggressive many children succumb to side effects rather than the cancer itself.
“The research findings are really uplifting, yes,” said Taylor, “because for so many clinicians like myself, we see children dying in front of us.” Taylor said the 140 scientists involved in the Medullo-blastoma Advanced Genomics International Consortium (MAGIC) – including 20 from B.C. – will continue their investigation into the childhood cancer in hopes of developing more targeted treatment.
He added, however, that drug trials on previously unused chemo agents will have to be largely publicly financed because pharmaceutical companies are wary of sponsoring research in pedi-atric cancers.
“Drug companies don’t care that much about doing it [research and development in pediatric cancers] because these are rare cancers and they’re worried about the liability in testing in children, because they could be on the hook for billions of dollars [if things go wrong],” he said.
