B.C. scientists discover why new drugs fail for children with recurrent brain cancer
Researchers say the study's findings could change the way new and experimental drugs are tested in children.
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Canadian scientists have uncovered why new and experimental drugs fail for children with recurrent medulloblastoma, a common and often fatal type of childhood brain cancer.
The authors of the study, co-led by the BC Cancer Agency and Sick Kids in Toronto, say the findings offer a simple explanation that could change the way drugs are tested in children.
“Basically, we’ve been idiots for the last 30 or 40 years, but now we have a really simple answer for why nothing worked,” said Dr. Michael Taylor, neurosurgeon at Sick Kids and co-principal investigator of the study. “I hope we can stop wasting time and putting all those poor little kids and their families through clinical trials for nothing, and finally find some things that help.”
Medulloblastoma, the most common cancerous brain tumour in children, is known to be difficult to successfully treat. Side effects of treatment, like chemotherapy, radiation and surgery, can have a devastating impact on a child’s brain, leaving them with significant disabilities. Almost 30 per cent of cases result in a recurrence of the tumour, which is nearly always fatal.
Part of the problem is that almost all research done to understand the biology of childhood brain cancer and to identify new drugs that might work has been carried out using tumour tissue taken during surgery before the child undergoes treatment.
Any experimental drugs that are identified as possible treatments are then tested in clinical trials involving children who have already undergone extensive chemotherapy.
“That’s been based on a really stupid assumption— in retrospect, stupid— that the tumour at the time when it comes back is the same as the tumour when we’re first diagnosing,” said Taylor. “And it’s not.”
Using genome sequencing to test tumour samples in both mice and children— one taken at diagnosis and another at the time of recurrence— the researchers found the genetic makeup of the tumours at the time of diagnosis had significantly transformed when the cancer came back.
Only about 10 per cent of the mutations found initially were still there in the recurrent tumour, said Taylor.
“That means if you … discovered a way to treat the tumour and you found a drug for it, the chances of it working would probably be less than one in 10,” he said. “It’s like trying to make orange juice out of apples.”
Dr. Marco Marra, distinguished scientist at the BC Cancer Agency, said the study’s findings highlight a need to identify treatment that might be effective in treating recurrent tumours— not just for medulloblastoma but other types of cancer, as well.
“There are many, many other types of cancers that behave in this particular way,” he said. “There have been several studies … which have alluded to the fact that cancers are not static entities … This business of cancer being an entity that evolves is actually critically important.”
The study was published Wednesday in the online edition of the journal Nature.