April 17, 2019
Collaborative research group identifies new cancer-driving mechanisms in brain cancer stem cells, describes novel ways to overcome the limited effectiveness of standard therapy
Glioblastoma is the most common and the most deadly type of brain cancer found in adults, yet there have been no new advances in treating this disease for almost two decades. Recent research has provided a wealth of knowledge about the genomics – or the abnormal genetic code – of glioblastoma, but this has yet to translate into new treatments for patients. Understanding which genes drive glioblastoma can help uncover new ways to treat this incurable disease, and a pan-Canadian research group has set out to do just that.
Researchers from the University of Toronto, The Hospital for Sick Children and the University of Calgary have teamed up to identify genetic vulnerabilities in brain cancer stem cells – the cells that often resist treatment and cause the disease to return in patients after treatment. Their recent findings, which were published today in Cell Reports, uncovered new targets for glioblastoma and unraveled some of the complex mechanisms behind the disease.
“We set out to understand which genes are important functionally,” says Dr. Graham MacLeod, co-primary author of the study and Research Associate in the lab of Dr. Stéphane Angers at the University of Toronto. “Connecting a gene to its function is a bit like connecting circuits on a very complex circuit board. If we can understand which genes are important, then we can find hints into where to unplug, plug in, stop and start mechanisms so that we can potentially stop the progression of the disease.”
The group used CRISPR-Cas9 gene editing tools, which Angers and MacLeod specialize in, to investigate all 20,000 genes within the genome and identify the key genes that are required for glioblastoma cells to survive and grow. In their study, they identified one gene in particular whose function is already targeted in leukemia treatments. Angers says this is promising “because it uncovered a biological process, not previously suspected to be implicated in glioblastoma, for which a small molecule drug already exists.”
As part of OICR’s Brain Cancer Translational Research Initiative, the next stage of their research will use the same gene editing approach to investigate tumour cells after therapy to find the genes or the genomic changes that help tumour cells evade treatment and recur in patients.
Read more about this research on University of Toronto News or learn more about the Stand Up To Cancer Canada Cancer Stem Cell Dream Team.
November 2, 2017
Biomarkers that can help predict a patient’s response to a given drug are central to testing new therapies in clinical trials as well as selecting which drugs to use in the clinic. Some of the biomarkers in use today rely on the overall expression of a given gene to predict if a drug will be of benefit. While these types of biomarkers have aided cancer research and treatment, a group led by Dr. Benjamin Haibe-Kains recently published research that is ushering in a new class of biomarkers – those based on gene isoforms (the different expression of the same gene within an individual). This work opens the door to more precise biomarkers.
August 30, 2017
An international team of scientists have used an innovative barcode-like system to track the behaviour of individual glioblastoma cells, allowing them to see how the cells of this deadly form of brain cancer have successfully evaded treatment and how they spread.
February 4, 2016
Stand Up To Cancer Canada Announces New Cancer Stem Cell Dream Team To Attack Brain Cancer in Children and Adults
Pan-Canadian Team of Researchers Will Receive CA $11.7 Million in Funding from Stand Up To Cancer Canada, Genome Canada, Canadian Institutes of Health Research, Cancer Stem Cell Consortium, and Ontario Institute for Cancer Research
February, 4, 2016—TORONTO—A team of top Canadian scientists, including leading pioneers of stem cell research, was named today to lead a new attack on brain cancers in children and adults, using genomic and molecular profiling technologies to focus on the cancer stem cells that drive the growth of tumours.
“Brain tumours are not as common as many other forms of cancer, but they are devastating, especially when they strike the very young,” said Phillip A. Sharp, PhD, Nobel laureate and institute professor at the Massachusetts Institute of Technology’s David H. Koch Institute for Integrative Cancer Research and co-chair of the Stand Up To Cancer (SU2C) Canada Scientific Advisory Committee (SAC). “The Dream Team will bring new insights to brain cancer research, which has been an underfunded area.”
December 22, 2015
The first Stand Up to Cancer (SU2C) Canadian Dream Team of researchers was announced September 30, with $9 million provided over four years to support Canadian research on aggressive types of breast cancer.
The team, led by Dr. Tak Mak at the Princess Margaret Cancer Centre, will be developing new therapies aimed at changes in the genomes of cancer cells that make breast cancer tumours unstable and vulnerable to attack – the so-called “Achilles’ heel” of aggressive breast tumours. The researchers will test three candidate drugs and hope to identify biomarkers that will help to better personalize treatment for patients.