September 30, 2019
McMaster University researcher and OICR Investigator, Dr. Kristin Hope, turns her stem cell discovery into a new treatment approach for leukemia.
A few years ago, Dr. Kristin Hope and her research team discovered a new way to grow rare life-saving blood stem cells. Now, the Hope Lab is using this discovery to suppress leukemic stem cells – the cells at the “root” of leukemia.
In their most recent study, published earlier this month in Cancer Research, the Hope Lab discovered that the same molecular pathway they found previously could be turned off to grow healthy stem cells could be turned on to impair the development of cancer stem cells.
The study suggests that this pathway, called the aryl hydrocarbon receptor (AHR) signaling pathway, could be leveraged as a potential therapeutic approach for acute myeloid leukemia – one of the most common subtypes of leukemia.
“We saw a loss of leukemic stem cells by activating – or turning on – the AHR pathway,” Hope says. “This brings us a step closer to a potential new therapy for patients with leukemia.”
The study group used a small molecule to activate the AHR pathway, finding that it had a significant effect in eliminating leukemic stem cells, but no effect on healthy cells. The group found similar results in cell cultures as well as in mice that were transplanted with human leukemia cells.
Hope, who is a Principal Investigator at McMaster University’s Stem Cell and Cancer Research Institute, will continue investigating this small molecule as a potential drug that could complement chemotherapies in the future.
“We will continue building on our understanding of the AHR pathway and how to control it,” she says. “This understanding will help us in the development of new therapies so that our discoveries can one day help patients.”
April 24, 2019
Collaborative research group discovers a key pathway in the development of acute myeloid leukemia – and a potential new therapeutic strategy to treat the disease
Despite progress in the treatment of acute myeloid leukemia (AML), many patients still die from relapse or experience significant side effects from treatment. Dr. Aaron Schimmer, who is Research Director of the Princess Margaret Cancer Centre and co-lead of OICR’s Acute Leukemia Translational Research Initiative, worked with his collaborators to understand the root cause of AML relapse to develop more effective and less toxic therapies. Their recent findings are both surprising and promising.
The group, which consists of researchers from across Ontario and abroad, investigated the pathways that are uniquely important to the growth and development of leukemic stem cells (LSCs) – also known as the cells at the “root” of the disease. They discovered a key pathway, as described in Cell Stem Cell, which can be altered to control how LSCs mature. Interestingly, they found that this process can be modulated with an essential phospholipid (a type of fat), called phosphatidylserine.
“We discovered a pathway that these stem cells rely on. We investigated further and found that interfering with lipid metabolism – that is, the fats within these cells – could potentially slow their growth and reduce their ability to cause relapse,” says Ayesh Seneviratne, MD/PhD candidate in the Schimmer Lab at the University of Toronto and co-first author of the publication.
Normally, phosphatidylserine is important in maintaining the integrity of the cell membrane and normal cell function, but the authors found that within LSCs, phosphatidylserine acted as a trigger for the cell to lose its self-renewal properties. They are the first group to describe increasing phosphatidylserine as a potential therapeutic strategy for AML.
“We now better understand the function of this metabolite in leukemia, and in turn, we have found a new way to target the disease,” says Dr. Mingjing Xu, postdoctoral fellow in the Schimmer Lab and co-first author of the publication. “We are enthusiastic to pursue further studies and unravel how phosphatidylserine ceases leukemia growth.”
Schimmer says that this work could not have been done without the contributions of many collaborators.
“This discovery is a product of a concerted effort between many researchers,” says Schimmer. “Together, we’ve found new insights into the biology of leukemia and turned those insights into a new potential therapeutic strategy.”
January 29, 2019
First-in-class drug for blood cancers discovered by Ontario researchers receives record-setting industry investment
Years of hard work by OICR’s Drug Discovery group and Ontario partners moves potential new treatment for leukemia towards clinical trials
On January 29, 2019, Celgene Corporation made an investment of up to US$1 billion that will facilitate further research and development of the potential drug and support clinical trials in Ontario. The potential drug was designed to exploit a weakness in leukemia centred on the protein WDR5 that was discovered by Ontario researchers. If all options under the investment are exercised, the deal will be the largest transaction to date for a preclinical asset discovered in Canada.
“The progress of this pre-clinical drug towards the clinic is an example of how OICR, working with its partners, is accelerating cancer research in Ontario and increasing investment so that new innovations can help patients as soon as possible,” says Dr. Laszlo Radvanyi, President and Scientific Director of OICR. “This announcement shows how OICR and FACIT’s unique model for research and commercialization can generate long-term impact for the province of Ontario.” FACIT is OICR’s strategic commercialization partner.
The WDR5 project’s development demonstrates the unique expertise of OICR DD, the advantages to the OICR-FACIT model, and how OICR effectively harnesses the strengths of Ontario’s diverse cancer research ecosystem by collaborating with groups such as the Structural Genomics Consortium (SGC), the group that initially identified the potential of targeting WDR5 as a treatment for cancer.Continue reading – First-in-class drug for blood cancers discovered by Ontario researchers receives record-setting industry investment
August 7, 2018
Big data are ushering in a new era of individualized cancer care and prevention, but not without conceptual and practical challenges. Canadian advances in genomics will be made by or limited by bioinformatics analytical capacity as well as the ability to store and analyze data in new and more sophisticated ways.
To help realize the potential of genomics research in cancer, the Canadian Data Integration Centre (CDIC) platform, led by OICR, offers third generation bioinformatics and genomics tools to support both functional and clinical genomics research. CDIC is the largest academic cancer informatics program in the country – offering customizable, client-oriented access services for data challenges across diverse research areas.
July 10, 2018
Acute myeloid leukemia (AML) progresses quickly and requires treatment soon after diagnosis, but the disease begins long before becoming symptomatic. Early indicators of AML were thought to be indistinguishable from healthy aging. But now, an international group of researchers led in part by Dr. Sagi Abelson, a postdoctoral fellow in the lab of Dr. John Dick at the Princess Margaret Cancer Centre, has discovered distinctive traces of AML in patients up to 10 years before they were diagnosed with the disease.
October 20, 2017
Researchers have discovered a new potential treatment for acute myeloid leukemia (AML). They found that boosting fat cells (adipocytes) within bone marrow with the use of a common diabetes drug slowed the growth of cancerous cells and promoted the regeneration of healthy blood cells.
July 11, 2017
The rising use of stem cell-based therapies has illustrated the power of stem cells to treat a number of diseases. Now a group of Ontario researchers are looking at the promise of stem cells from a different perspective. Amongst other efforts, they are developing and testing new therapies that target and kill leukemic stem cells to lessen the chances of acute leukemias (AL) coming back following standard treatment.
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.
May 25, 2017
OICR launches five all-star teams of Ontario scientists to tackle some of the deadliest forms of cancer
Great strides have been made in cancer research, but much work remains to develop better treatments for the most lethal cancers and to advance new anti-cancer technologies. OICR is taking on a new approach, building on the success of the Institute’s first ten years and Ontario’s strength in particular cancer research areas. Reza Moridi, Ontario’s Minister of Research, Innovation and Science announced that the Institute is funding five collaborative, cross-disciplinary and inter-institutional Translational Research Initiatives (TRIs) with a total of $24 million over the next two years.
The TRIs will bring together some of the top cancer researchers in Ontario and be led by internationally renowned Ontario scientists. Each team will focus on a certain type of cancer or therapeutic technology. To maximize the positive impact of research on patients, the TRIs all incorporate clinical trials into their design. The TRIs, which were selected by an International Scientific Review Panel, are:
- Acute Leukemia TRI (led by Drs. John Dick and Aaron Schimmer at the University Health Network (UHN))
- Brain Cancer TRI (led by Drs. Peter Dirks and Michael Taylor at SickKids)
- Immuno-oncology TRI (ACTION) (led by Drs. John Bell and Marcus Butler at The Ottawa Hospital and UHN)
- Ovarian Cancer TRI (led by Drs. Amit Oza and Rob Rottapel at UHN)
- Pancreatic Cancer TRI (PanCuRx) (led by Dr. Steven Gallinger at UHN)
The funding will also support Early Prostate Cancer Developmental Projects led by Drs. Paul Boutros and George Rodriguez.
“In just over 10 years, the Ontario Institute for Cancer Research has become a global centre of excellence that is moving the province to the forefront of discovery and innovation in cancer research. It is home to outstanding Ontario scientists, who are working together to ease the burden of cancer in our province and around the world,” said Moridi.
“Collaboration and translational research are key to seeing that the innovative technologies being developed in Ontario reach the clinic and help patients,” said Mr. Peter Goodhand, President of OICR. “These TRIs represent a unique and significant opportunity to impact clinical cancer care in the province.”
— SickKids_TheHospital (@SickKidsNews) May 25, 2017
— UHN (@UHN_News) May 25, 2017
— The Ottawa Hospital (@OttawaHospital) May 25, 2017
May 25, 2017
OICR launches five large-scale Ontario research initiatives to combat some of the most deadly cancers
Toronto (May 25, 2017) – Reza Moridi, Ontario’s Minister of Research, Innovation and Science, today announced the Ontario Institute for Cancer Research is launching five unique, cross-disciplinary, multi-institutional Translational Research Initiatives (TRIs), each focused on a single type of or treatment approach to cancer. With $24 million in funding over two years, the TRIs will bring together world-leading scientists to tackle some of the most difficult to treat cancers and test innovative solutions to some of the most serious challenges in cancer today.
The TRIs build on Ontario’s proven strengths in areas such as stem cells, immuno-oncology, pediatric cancers, genomics, clinical trials and informatics. Working together, the province’s top scientists and clinicians will accelerate the development of much needed solutions for patients around the globe, with a focus on acute leukemia and brain, ovarian and pancreatic cancers. Each TRI includes clinical trials to maximize patient impact.
April 25, 2017
Dr. John Dick was recognized for his pioneering research in cancer stem cells with the presentation of the CIHR Gold Leaf Award for Discovery. He was the first scientist in the world to confirm their existence. Better understanding of cancer stem cells has the potential to lead to new treatments, ultimately resulting in improved patient outcomes.
December 7, 2016
Acute myeloid leukemia (AML) is the most common form of acute leukemia in adults and is one of the most deadly. Although AML is treated as a single disease, patient response to intensive curative-intent chemotherapy varies. It is currently difficult to predict who will do well with standard treatment, and who will not benefit from standard treatment and might do better enrolling in a clinical trial where they may be offered novel therapies.