July 17, 2019
Collaborative research group maps the three-dimensional genomic structure of glioblastoma and discovers a new therapeutic strategy to eliminate cells at the roots of these brain tumours
Current treatment for glioblastoma – the most common type of malignant brain cancer in adults – is often palliative, but new research approaches have pointed to new promising therapeutic strategies.
A collaborative study, recently published in Genome Research, has mapped the three-dimensional configuration of the genome in glioblastoma and discovered a new way to target glioblastoma stem cells – the self-renewing cells that are thought to be the root cause of tumour recurrence.
The research group integrated three-dimensional genome maps of glioblastoma with other chromatin and transcriptional datasets to describe the mechanisms regulating gene expression and detail the mechanisms that are specific to glioblastoma stem cells. They are one of the first groups in the world to perform three-dimensional genomic analyses in patient-derived tumour samples.
“The 3D configuration of the genome has garnered much attention over the last decade as a complex, dynamic and crucial feature of gene regulation,” says Dr. Mathieu Lupien, Senior Scientist at the Princess Margaret Cancer Centre, OICR Investigator and co-author of the study. “Looking at how the genome is folded and sets contacts between regions tens to thousands of kilobases apart allowed us to find a new way to potentially tackle glioblastoma.”
Through their study, the group discovered that CD276 – a gene which is normally involved with repressing immune responses – has a very important role in maintaining stem-cell-like properties in glioblastoma stem cells. Further, they showed that targeting CD276 may be an effective new strategy to kill cancer stem cells in these tumours.
Lupien adds that advancements in three-dimensional genomics can only be made through collaborative efforts, like this initiative, which was enabled by OICR through Stand Up 2 Cancer Canada Cancer Stem Cell Dream Team, OICR’s Brain Cancer Translational Research Initiative and other funding initiatives.
“This research was fueled by an impressive community of scientists in the area who are committed to finding new solutions for patients with brain cancer,” Lupien says. “Our findings have emphasized the significance of three-dimensional architectures in genomic studies and the need to further develop related methodologies to make sense of this intricacies.”
Senior author of the study, Dr. Marco Gallo will continue to investigate CD276 as a potential therapeutic target for glioblastoma. He plans to further delineate the architecture of these cancer stem cells to identify more new strategies to tackle brain tumours.
“A key problem with current glioblastoma treatments is that they mostly kill proliferating cells, whereas we know that glioblastoma stem cells are slow-cycling, or dormant. Markers like CD276 can potentially be targeted with immunotherapy approaches, which could be an effective way of killing cancer stem cells, irrespective of how slowly they proliferate,” says Gallo, who is an Assistant Professor at the University of Calgary. “Being able to kill cancer stem cells in glioblastoma could have strong implications for our ability to prevent relapses.”
June 10, 2019
OICR-supported researcher Dr. Nicole Mittmann leads collaborative initiative to determine the value of new cancer solutions and the burden of cancer care on Canada’s healthcare system
Canada is well known for its publicly funded healthcare system, its universal health coverage, and in most recent news – for the Toronto Raptors.
What is less recognized, however, is that with its distinctive healthcare system, Canada has unique healthcare reimbursement processes and resource needs, especially for the delivery of cancer care. While Canada collects some of the most robust and comprehensive healthcare data, Canadian datasets are underutilized in research and policy decision making.
Dr. Nicole Mittmann has set out to close this gap and, in turn, transform our administrative health information into tangible healthcare improvements.
“As cancer-drug costs continue to rise, there is – now more than ever before – a need to understand the Canadian context with respect to costs and health system resource use,” she writes in Current Oncology.
Turning data into action
Mittmann, who was recently appointed as the Chief Scientist and Vice-President of Evidence Standards at the Canadian Agency for Drugs and Technologies in Health (CADTH), sees Canada’s rich data as a goldmine for improving the management of diseases and the delivery of care.
“This information can be used to help us make decisions, help us plan and help us understand the value of new technologies,” she says. “It could also show us areas where we need to improve, or problems that weren’t apparent through practice alone, but we needed to reduce the barriers to using these data for research.”Continue reading – It’s our health information: a goldmine for improving the quality of cancer care
June 4, 2019
New research projects to drive clinical adoption of novel cancer technologies and find ways to better deliver cancer services
10 projects to receive funding through OICR-CCO Health Services Research Network
Toronto (June 4, 2019) – The Ontario Institute for Cancer Research (OICR) today announced funding for 10 projects as part of the OICR-Cancer Care Ontario (CCO) Health Services Research Network (HSRN). As part of the HSRN, these projects are focused on optimizing the delivery of existing cancer services and guiding the dissemination of new practices and technologies in cancer prevention, screening and care in Ontario.
The funded projects, which involve 103 researchers and clinicians based at 29 institutions across Ontario, as well as five institutions outside of the province, focus on at least one of six priority areas: using real-world evidence to advance innovations; data infrastructure, integration and mobilization studies; use of artificial intelligence and digital health tools; the adoption of accepted best practices related to precision medicine; knowledge translation and dissemination; and population health studies.
“Improving the delivery of cancer-related healthcare and ensuring that new innovations are properly introduced into clinical use is an essential part of improving outcomes for cancer patients,” says Dr. Christine Williams, Deputy Director and Interim Head, Clinical Translation, OICR. “The projects funded today will help integrate more leading-edge technologies and practices – such as artificial intelligence, immunotherapies and precision medicine – into Ontario’s healthcare system. OICR is proud to help enable improvements in frontline care for the people of Ontario through these projects.”
In total, the projects announced today will receive more than $2.7 million in funding over the next two years. These projects were awarded funding after a competitive process, including review by an expert panel. Together, these projects are a key arm of OICR’s Clinical Translation initiative, which is driving the translation of research findings into patient impact by partnering with the healthcare system.
“I congratulate the researchers who have received funding today and laud their efforts to optimize how we prevent, diagnose and treat cancer in Ontario,” says Hon. Merrilee Fullerton, Ontario’s Minister of Training, Colleges and Universities. “As new technologies and best practices emerge, it is important that Ontario use its research expertise to deliver these advancements to the people as quickly and efficiently as possible.”
For details about the funded projects please visit: https://oicr.on.ca/research-portfolio/health-services-research/Continue reading – New research projects to drive clinical adoption of novel cancer technologies and find ways to better deliver cancer services
May 30, 2019
Meta-analysis of 1,200 patients with pancreatic cancer reveals a new way to identify those with very aggressive tumours who may benefit from alternate treatment approaches
Only half of pancreatic cancer patients who undergo standard chemotherapy and surgery live a year after their initial diagnosis. In the face of these dismal statistics, patients are faced with the challenge of deciding whether they want to proceed with treatment that may have unpleasant side effects. If clinicians could identify patients who would not benefit from standard therapies, they could help these patients make more informed treatment decisions or recommend alternative palliative treatment approaches.
As part of OICR’s Pancreatic Cancer Translational Research Initiative (PanCuRx) team led by Dr. Steven Gallinger, Dr. Benjamin Haibe-Kains recognized that computational modeling can be used to help inform these decisions, but to design a robust predictive model he would need much more data than any individual study had ever collected.
Building the data foundations
Haibe-Kains, who is a Senior Scientist at the Princess Margaret Cancer Centre and OICR Associate, began his investigation with a dataset from PanCuRx – the largest collection of genomic and transcriptomic data on primary and metastatic pancreatic tumours to date. He and his lab then incorporated an additional 1,000 cases of pancreatic tumours from studies around the world that had collected both patient samples and information about how each patient responded to treatment.
“The datasets that we aggregated were a mixed bag of different types of data collected through different profiling platforms by different institutions,” says Haibe-Kains. “We took on the challenge of harmonizing the heterogeneity of these resources which nobody else had done.”
Previously, the Haibe-Kains Lab developed a computational method that could make incompatible transcriptomic data compatible. They had used this method to find four new breast cancer biomarkers to predict treatment response and they recognized that they could apply similar methods to harmonize pancreatic cancer data as well.
The dataset resulting from the harmonization is now the largest pancreatic cancer dataset, and Haibe-Kains has made it freely available for other researchers to use and study through the MetaGxPancreas package.
Making a predictive model
Haibe-Kains and his team set out to develop a computational model that could predict if a patient would survive for a year after their biopsy. They used machine learning techniques to exploit their rich dataset, find common patterns in the genomic data of aggressive tumours, and developed PCOSP – the Pancreatic Cancer Overall Survival Predictor.
“Our approach was to look at how one gene was expressed relative to another and relate that to how long a patient lived after biopsy,” says Haibe-Kains. “That may sound simple, but that means dealing with nearly 200 million pairs of genes, which is a significant amount of data to compute.”
As recently described in JCO Clinical Cancer Informatics, the group refined PCOSP using ensemble learning – the combination of several machine learning techniques to improve a model’s accuracy of predictions.
“PCOSP is actually a combination of hundreds of models and not just one,” says Haibe-Kains. “We tested about a thousand models, selected the models that could predict early death very well and combined them to make a stronger classifier.”
Using prediction to power patient decisions
Haibe-Kains says that as the infrastructure for routine sequencing progresses, PCOSP can be translated into clinical practice to help clinicians determine which patients would not benefit from standard treatment and which may benefit from alternative treatment approaches.
“Pancreatic cancer is a challenging disease but if we can predict the course of the disease, we can give clinicians and patients more information. With that information, they can make more personalized decisions to improve their treatment and ideally, their lives.”
September 10, 2018
Hamilton researchers discover that cancer stem cells may not be the only culprits of acute myeloid leukemia relapse
Although current chemotherapy for acute myeloid leukemia (AML) is effective in the short term, the disease often returns a few years after treatment. A new study suggests that the relapse of leukemia may not be caused by leukemic stem cells – a special set of cells that can avoid initial treatment by not dividing, then give rise to new cancerous cells after therapy – but rather a different class of leukemic cells.
August 16, 2018
Ottawa researchers discover a new way to make cancer cells more susceptible to virus-based therapies
Over the past decade, researchers have made significant progress in designing oncolytic viruses (OVs) – viruses that destroy cancer cells while leaving healthy tissue unharmed. However, some cancer cells are resistant to this type of therapy and their resistance mechanisms remain poorly understood.
Researchers at the The Ottawa Hospital and University of Ottawa, under the leadership of Dr. Carolina Ilkow, have discovered that a common cellular mechanism, RNAi, allows cancer cells to fight back against cancer-fighting viruses. Their findings, recently published in the Journal for Immunotherapy of Cancer, show that blocking RNAi processes in tumours can make cancer cells more susceptible to OVs.
July 11, 2018
New funding for the Canadian Cancer Clinical Trials Network will help more cancer patients access clinical trials
Toronto (July 11, 2018) – The Ontario Institute for Cancer Research (OICR) and the Canadian Partnership Against Cancer (the Partnership) today announced renewed funding for the Canadian Cancer Clinical Trials Network (3CTN). The funding will ensure Canada remains a world leader in academic cancer clinical trials, help to increase opportunities for patients to receive promising new treatments and continue to improve outcomes for cancer patients through research.
July 9, 2018
The BETTER program has been awarded almost $3 million to train primary care providers as prevention experts across Canada
As the number of Canadians at risk of cancer and other chronic diseases continues to grow, so does the need for health professionals to deliver effective disease prevention and screening recommendations.
March 8, 2018
OICR’s Brain Cancer Translational Research Initiative (TRI) and the Terry Fox Precision Oncology for Young People Program (PROFYLE) are partnering to share data and deliver improved treatment options to young brain cancer patients.
January 30, 2018
Early results from COMPASS trial demonstrate benefits of using genomic sequencing to guide treatment for pancreatic cancer
Genomic profiling has allowed physicians to customize treatments for patients with many types of cancer, but bringing this technology to bear against advanced pancreatic cancer has proven to be extremely difficult. OICR’s pancreatic cancer Translational Research Initiative, called PanCuRx, has been conducting a first-of-its-kind clinical trial called COMPASS to evaluate the feasibility of using real time genomic sequencing in pancreatic cancer care. The research team recently reported early results from the trial, which show how they overcame the challenges of genomic profiling specific to pancreatic cancer and gained new insights about the disease.
PanCuRx is focused on improving treatment for pancreatic adenocarcinoma (PDAC), the most common form of pancreatic cancer and the fourth leading cause of cancer death in Canada. The group’s approach centres around understanding the genetics and biology of PDAC to inform the selection of therapies, as well as the development of new treatments.
September 6, 2017
Today’s therapies for medulloblastoma, a highly aggressive form of childhood brain cancer, bring benefits to young patients but also come with serious side effects. Dr. Michael Taylor and a team of international collaborators recently published results in Nature of an ambitious project that analyzed the genomes of around 500 cases of medulloblastoma. Their goal was to identify gene mutations that are commonly mutated in the cancer, but not in the normal cells of patients.
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.