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VANCOUVER – Canadian researchers have identified genes in brain cancer stem cells that fuel the growth and survival of glioblastoma in the hope that their data will be used to develop treatments targeting an aggressive tumor that would have cost the lives to Gord Downie, leader of Tragically Hip.
The main challenge lies in the fact that even after eliminating 99% of a tumor, some remaining cells multiply like tentacles and regenerate in another part of the brain where surgery does not occur. is more feasible.
Dr. Peter Dirks, co-principal investigator of a study published Tuesday in the journal Cell Reports, said that despite genomic research that has led to better drug treatments for various cancers over the last decade, few progress has been made in the treatment of glioblastoma. remained largely a mystery.
"It's a miserable path because your brain is deprived of your identity," said Dirks, who in 2003 discovered the existence of cancer stem cells in brain tumors and one of whose relatives died of glioblastoma.
"It happened a few years ago certainly continued to strengthen my commitment to do our best to keep trying to get things done," said the neurosurgeon and senior scientist in brain tumor research at the University of Toronto. Children's Hospital of Toronto.
The findings of the study, which includes research conducted by Dirks and researchers at the Leslie Dan School of Pharmacy at the University of Toronto and the Cumming School of Medicine at the University of Calgary, could help scientists around the world offer new drugs that go beyond the standard for most ineffective radiotherapy and chemotherapy treatments, said Dirks.
His research team provided 10 glioblastoma stem cell cultures to an experiment using a powerful genetic technology called CRISPR-Cas 9 to analyze the 20,000 genes in each of the patient samples to determine which ones are important for proliferation and reproduction. growth of glioblastoma cells.
Dr. Stephane Angers, co-principal investigator of this part of the study at the University of Toronto, said that the Cas9 protein appears to be a reference device that targets certain important genes for the progression of tumor 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 engine parts are important to move the car forward.Our study basically identified the engine parts, which are the parts in the cells that are really important for cell growth. tumor. "
The technology could someday allow Cas9 to cut off and disable the "bad" genes, thus replacing disease-causing DNA mutations with new DNA sequences.
"We found about 400 important genes for the growth and lifespan of these glioblastoma tumor cells, so we need to target these to a subgroup of candidates for a new drug, and I would say that 20 to 30 out of 30 for sure, "said Angers.
"We and others are now going to try to develop inhibitors, drugs, small molecules and antibodies to interrupt the functioning of these genes.What we are now providing to the scientific community, is the book blue, if you will, the instruction manual of how our cancerous glioblastoma cells are wired and what is important in their circuits to drive growth programs. "
Of the thousands of genes analyzed, one called DOT1L was found necessary for tumor persistence in seven cultures of 10 patients.
Dr. Samuel Weiss of the Calgary School of Medicine has demonstrated that the same gene is also involved in the growth of certain leukemias, for which a particular drug is currently used as a treatment.
Angers said the drug does not fit well in the brain and so it could not be tested immediately in patients with glioblastoma, although it may possibly be modified to improve its administration. brain and conduct clinical trials to determine its usefulness.
Dirks and Angers said that although their study suggested a tailor-made treatment in the future, they warned that there was still much work to be done to develop glioblastoma puzzle pieces while researchers were struggling with the disease that also cost the NDP member his life. Paul Dewer, along with US Senators John McCain and Ted Kennedy, and the son of former Vice President Joe Biden, Beau Biden.
The survival rate is about eight percent over five years for the disease diagnosed each year among about 1,500 Canadian adults and 150 children. The average survival time after diagnosis is about 14 months.
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