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.”
July 3, 2019
The Lebovic Fellowship program connects scientists in Israel and Ontario, leading to the validation of a new drug candidate for leukemia and the optimization of a new potential cancer vaccine
Three years ago, the Institute for Medical Research Israel-Canada (IMRIC) received a donation from Joseph and Wolf Lebovic – two brothers who are Holocaust survivors, Canadian immigrants, avid philanthropists and recently-appointed Members of the Order of Canada. Their vision was to strengthen collaboration between the outstanding researchers in Israel and those in Ontario to accelerate cancer research.
They created the Joseph and Wolf Lebovic Fellowship Program, which paired together laboratories specializing in complementary subjects. The Program’s first round of projects officially came to a successful close today and here we recognize the progress made thanks to the generous donation of the Lebovic brothers.
Developing a drug for leukemia
Israel lead researcher: Dr. Yinon Ben-Neriah, IMRIC
Israel fellows: Waleed Minzel and Eric Hung, PhD Candidates, Hebrew University of Jerusalem
Ontario lead researcher: Dr. John Dick, Princess Margaret Cancer Centre (PMCC)
Ontario fellow: Dr. Laura Garcia-Prat, Postdoctoral Fellow, PMCC
Ben-Neriah’s lab in Israel had developed a new compound and showed it may be a valuable anti-leukemia drug, but they couldn’t explain why the drug was only effective in animal models that had strong immune systems. Understanding the relationship between the drug and the immune system would allow them to validate which leukemia subtypes would respond to their therapeutic approach.
John Dick’s lab had developed the gold standard for evaluating the efficacy of leukemia drugs in animal models using sophisticated patient-derived xenograft mouse models. Through this fellowship, the Ben-Neriah Lab teamed up with the Dick lab to learn from their expertise and gain insights into their experimental models.Continue reading – Five fellows, four labs, three years, two countries, and a generous donation
March 19, 2019
Collaborative research group performs the most comprehensive analysis of curable prostate cancer to date, finds key connections between different data types
As cancer researchers delve deeper into different omics studies, and technologies enable their ability to do so, it is becoming increasingly important to understand how these areas of research are interconnected. Previous studies across multiple omes – such as the genome, proteome, transcriptome or epigenome – have led to important discoveries in colorectal cancer and ovarian cancer, but prostate cancer remains largely unresolved. Researchers from the Canadian Prostate Cancer Genome Network (CPC-GENE) set out to unravel some of these mysteries.
In the most recent CPC-GENE study, published today in Cancer Cell, the research group integrated multiple levels of omics analyses to better understand the biology of intermediate-risk prostate cancer – a type of cancer in which it is notoriously difficult to predict and treat accordingly. A better understanding of this disease could lead to improved tests that can determine which tumours are aggressive and require aggressive treatment, while helping spare those whose cancer will never become aggressive the negative side effects of treatment.
“We cannot overlook the important information that we gain from looking at the bigger picture,” says Julie Livingstone, bioinformatician at OICR and co-author of the study. “In this case, this means looking at prostate cancer from multiple angles – or multiple omes – to potentially find new markers of aggressive disease.”
The study explored 76 prostate cancer tumours and found new combinations of information that could act as a better predictor of a patient’s chance of relapse than any single piece of information alone. More specifically, they identified that the combination of protein and methylation data could, on average, predict the severity of a tumour better than looking at just the proteins – the proteome – or just the methylation patterns – the methylome – alone.
“Integrating datatypes is anything but straightforward, but it illuminates interesting aspects about prostate cancer that we haven’t seen before,” says Livingstone. “In the future, we intend to pursue our multi-omic investigation and translate this understanding into better tools to inform treatment selection for men with this disease.”
Find out more about research from the CPC-GENE project on OICR News.
October 16, 2018
OICR offers new CT calibration service as part of its Collaborative Research Resources portfolio
Using imaging devices to help make treatment decisions in the clinic requires rigorous testing, quality assurance and routine calibration of the imaging machinery. These standards are especially important when the imaging technology is novel or unique, such as in the case of perfusion imaging – a relatively new technique used to diagnose a cancer’s stage by showing how blood flows through the tumour.
August 22, 2018
OICR-developed software tool, Heliotrope, gains attention from the private sector for its potential to analyze large amounts of genomic information and inform clinical decision making
July 10, 2018
Researchers further clarify the role of epigenetic proteins in the development of breast cancer, and discover that inhibiting these proteins could prevent the disease in women at high risk.
December 4, 2017
OICR launches groundbreaking Cancer Therapeutics Innovation Pipeline to drive cutting-edge therapies to the clinic
Ten new projects were selected in the pipeline’s inaugural funding round, highlighting Ontario’s strengths in collaboration and drug discovery.
Toronto (December 4, 2017) – The Ontario Institute for Cancer Research (OICR) today announced the Cancer Therapeutics Innovation Pipeline (CTIP) initiative and the first 10 projects selected in CTIP’s inaugural round of funding. CTIP aims to support the local translation of Ontario discoveries into therapies with the potential for improving the lives of cancer patients. The funding will create a new pipeline of promising drugs in development, and attract the partnerships and investment to the province necessary for further clinical development and testing.
“Ontario congratulates OICR on this innovative approach to driving the development of new cancer therapies,” says Reza Moridi, Ontario’s Minister of Research, Innovation and Science. “The Cancer Therapeutics Innovation Pipeline will help ensure that promising discoveries get the support they need to move from lab bench to commercialization, and get to patients faster.”
September 6, 2017
Toronto (September 6, 2017) – Understanding a cancer’s genetics is key to selecting targeted therapies that are likely to be of the most benefit to a patient. The Ontario Institute for Cancer Research (OICR) today announced a new study, called Ontario-wide Cancer TArgeted Nucleic Acid Evaluation (OCTANE). OCTANE will use next-generation genome sequencing technology to bring a unified molecular profiling approach to five Ontario cancer centres.
August 9, 2017
Prostate cancer researchers have mapped the impact of an acquired mutation that alters epigenetic identity, the make-up of DNA, in about 50 per cent of patient tumour samples. The discovery also identifies a new opportunity for targeted therapy.
July 12, 2017
Given the advancements in treating many other types of cancer, it may come as a surprise that outcomes for patients with the most deadly form of ovarian cancer have not improved in 50 years. This form, known as High Grade Serous Ovarian Cancer (HGSOC), accounts for 80 per cent of ovarian cancer deaths in Canada. Surgery and chemotherapy can be effective, but ultimately three-quarters of women with HGSOC will see their disease return. To deliver better outcomes for patients, OICR has launched a new ‘all star team’ of ovarian cancer researchers.
July 11, 2017
The body’s immune system is incredibly powerful. Its ability to detect and destroy various pathogens makes it central to maintaining good health. While we all know the role it plays in fighting the common cold or flu, many do not know that it has recently been enlisted by scientists in the fight against cancer. Researchers in a field known as immuno-oncology are working to find ways to turn on the body’s defences to locate and destroy tumour cells. OICR recently established a team of expert scientists and clinicians to develop and test new immunotherapies to help patients.
June 28, 2017
By combining new knowledge from the fields of stem cell biology and genetics, a group of Ontario researchers led by Dr. John Dick have solved the mystery of why some acute myeloid leukemia (AML) patients relapse after initial treatment.