June 18, 2019
Toronto-based entrepreneur Zaid Atto receives FACIT’s Ernsting Entrepreneurship Award to further develop his new device for safer and less invasive surgeries
Ten years to the day after he and his family landed in Canada from Iraq, Zaid Atto stood in front of a panel of judges and pitched his idea. He had developed a new surgical device – a port that could allow for safer and more efficient minimally invasive surgeries – but he needed commercialization support and resources to move it into the next stage of development.
Surgeons use ports, also known as trocars, to make a tunnel into the body for laparoscopic surgeries. Complications with ports include accidental organ perforation, hernias and potentially death from incorrect insertions. Adding to the risk of complications, sometimes surgeons have to switch an inserted port for one with a larger diameter during the procedure to accommodate larger surgical instruments, or reinsert a port that slipped out of the abdomen accidentally. Through interviewing surgeons and shadowing dozens of surgeries, Atto recognized these concerns and saw an opportunity to address an unmet need and help both patients and surgeons.
After graduating with a biomedical engineering degree from the University of Toronto, Atto and his team at Xpan Inc. developed an expandable port that reduces the risk of complications associated with port insertion and alleviates the need to remove and reinsert ports. The team has consulted stakeholders and device manufacturers throughout the development of their device and have received support and validation from surgeons with multiple minimally-invasive surgical specialties.
“We saw that our device could assist surgeons across many subspecialties, especially those who have to exchange ports often, like in surgeries for colorectal cancer, pediatric surgeries or emergency procedures” says Atto. “Our port, however, is not limited to cancer surgeries. It’s a device that can make a difference for all laparoscopic surgeons and the five million patients who undergo minimally invasive surgery every year in North America.”
Earlier this year Atto pitched his technology at the FACIT Falcons’ Fortunes pitch competition. In addition to creating exposure for novel oncology innovations and providing training support for entrepreneurs, FACIT’s annual pitch competition celebrates a culture of commercialization in Ontario. Atto was one of six finalists who were pre-selected by the FACIT team to deliver pitches. Impressing the judges with an innovation developed based on a clearly-identified market need, Atto was ultimately awarded the $50,000 Ernsting Entrepreneurship Award. Xpan Inc. plans to use this funding to complete proof-of-concept animal studies and prepare for regulatory submission.
“By partnering with FACIT, we hope to bring our device one step closer to patients,” says Atto. “This means one step closer to safer and more efficient surgeries for all of us who may need these surgeries in the future.”
Read more about this story in FACIT’s most recent announcement of investments.
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 31, 2019
In May, OICR welcomed Dr. Trevor Pugh as Director of Genomics and Senior Principal Investigator. Trevor is a cancer genomics researcher and board-certified molecular geneticist who has led the Princess Margaret Cancer Centre-OICR Translational Genomics Laboratory (PM-OICR TGL) since 2016.
In his new role, he will lead the OICR Genomics program, which brings together the Princess Margaret Genomics Centre, OICR’s Genome Technologies, Translational Genomics Laboratory and Genome Sequence Informatics teams under an integrated initiative to support basic, translational and clinical research. Here, Pugh describes some of his strategies and how he plans to take on this ambitious mandate.
You’re involved with a number of projects across many disease sites and you collaborate with researchers from vastly different areas of cancer research. Can you summarize what you focus on?
Simply put – I want to use genome technologies to guide the best patient care. The overall philosophy is to extract as much genomic information as we can from small amounts of tumour tissue, and turn that information into knowledge so that clinicians and patients can make targeted treatment decisions. I also want to open up these comprehensive data for researchers to mine and find new cures for these cancers.
Whether they are a graduate student working on myeloma or a postdoc working on liver cancer, we all learn from one another’s disease specialties.
And yes – I am involved with many areas of cancer research. Every member in my lab speaks the same genomics language. Whether they are a graduate student working on myeloma or a postdoc working on liver cancer, we all learn from one another’s disease specialties. We do genomics in a similar way as there are many genomic commonalities across cancer types and computational algorithms or infrastructure we build for one project invariably get reused for another project.
You are a board-certified molecular geneticist and a genomics researcher, but you also have a background in bioinformatics and software development. How do you balance making tools and making discoveries?
The tools we create and the research we perform go hand in hand. You can’t make discoveries without the infrastructure, and it is hard to develop technologies successfully without a guiding scientific question. With that said, the software that we make is designed to help not only our own research and clinical projects, but those of others. If we can make software work for us really well, we want to share it and make it easier for groups and labs across Ontario and around the world. This also holds for the data we generate, as there is great value to integrating our data with similar data sets from other hospitals.
How will this new role help you do that?
I have a few main goals in this role that I’m excited about. The first and the largest is to integrate the Princess Margaret Genomics Centre, PM-OICR TGL, Genome Technologies and Genome Sequence Informatics into one fully-coordinated machine. The people, tools and methods that we have at OICR and Princess Margaret are incredible and the infrastructure already in place can serve as a powerful vehicle for both research and clinical applications. In the first two weeks, I’ve been really impressed with how the leads of these programs have come together to form concrete plans for making this a reality.
The part that excites me about my new role is the O in OICR. Within this position, I can have a provincial outlook on translational research which is important as genomics research becomes increasingly dependent on multi-centre studies and inter-institutional collaborations. I think OICR can help facilitate a future where sharing ideas, data, and knowledge between institutions is much easier than it is today. I’m excited to help take things that work locally and make them available and easy-to-use across the entire province, so that we can benefit from the advances made by our neighbours. We are stronger when we work together in a collaborative way.
OICR is well-known as a developer of similar high-quality data sharing systems and I am looking forward to integrating these efforts to support our internal genomics enterprise
It sounds like a lot of your work addresses local needs, but how do you have so many international collaborations?
In computational biology, a lot of our concerns and challenges are shared with other groups as well. For example, the cBioPortal data sharing platform was originally built at Memorial-Sloan Kettering to allow researchers to easily query data from The Cancer Genome Atlas project. This initiative soon grew to include a team at Dana-Faber and now the software is fully open-source with five core, NIH-funded teams contributing to its development, including my own lab. In addition, there are groups working on improving and enhancing cBioPortal instances around the world as it expands to new applications beyond genomics. cBioPortal has emerged as a very powerful resource rooted in an international crowdsourcing model. Naturally, OICR is well-known as a developer of similar high-quality data sharing systems and I am looking forward to integrating these efforts to support our internal genomics enterprise, as well as national and international data sharing networks.
You’ve been involved with the evolution of genomics over the last two decades. What technologies excite you these days?
Hands down, it’s single cell sequencing. This is an amazing technology that allows us to see parts of the tumours that we could never see before. In one of my projects, we’re looking at each cancer population within a tumour sample and mapping each population to a drug treatment. With Drs. Benjamin Haibe-Kains, we’re applying this concept across hundreds of thousands of cells from brain tumours we have sequenced in collaboration with Peter Dirks and from myeloma cells with Suzanne Trudel. If we can find distinct clones – or types of cells – with tailored treatment options, we could potentially eradicate the cancer entirely using combination therapies. I think the future of precision medicine is dependent on single cell technology and I look forward to integrating this technology into clinical studies with collaborators at cancer centres across the province.
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.”
May 27, 2019
Dr. Monika Krzyzanowska and collaborators develop app for cancer patients to manage and understand their treatment symptoms from the comfort of their own home
Patients undergoing cancer treatment face a lot of uncertainty. They often experience symptoms and treatment side effects at home, which often leads them to the emergency room. But in many cases, their side effects could have been better managed remotely and prevented from getting worse. Dr. Monika Krzyzanowska, Medical Oncologist at the Princess Margaret Cancer Centre, wanted a better option for her patients to understand and manage their symptoms comfortably at home.
“Almost half of women undergoing treatment for breast cancer visit the emergency room between treatment sessions and many of these visits can be avoided,” says Krzyzanowska. “We give our patients a lot of information up front, but we can do a better job at remote monitoring and providing them with the information they need when they need it. There’s a clear need for decision aids, self-management support, improved communication and options in care delivery.”
Krzyzanowska teamed up with the University Health Network’s Healthcare Human Factors team to explore how to improve symptom management for patients with a more personalized approach. In response to this need, they created bridges, a web-based app to facilitate remote management of chemotherapy-related side effects.
As recently described in the Journal of Medical Internet Research, the team refined their design over two rounds of usability testing with patients. They incorporated toxicity tracking, self-management advice and health care provider communication functionalities so that both physicians and patients can track and manage the patient’s symptoms.
With their pilot complete, Krzyzanowska is looking to partner with health care providers and decision makers to expand the project and explore how to integrate bridges into current systems and processes.
“Bringing bridges into the hands of patients is going to require a coordinated effort between decision makers, patients, care providers and hospitals,” says Krzyzanowska. “Helping patients who need it when they need it is our top priority and I look forward to developing bridges to help in that goal.”
Krzyzanowska’s project is one of the many research projects funded through OICR and Cancer Care Ontario’s Health Services Research Network.
May 21, 2019
Dr. Brigitte Thériault, a Senior Research Scientist at OICR, discusses the work of the Drug Discovery team to develop new drugs that awaken the body’s immune system to recognize and attack cancer cells.
May 17, 2019
OICR-supported trial finds new, more sensitive imaging technique can inform treatment decisions and benefit those with recurring prostate cancer
Prostate cancer is the most common type of cancer found in men, but managing the disease is difficult because not all prostate cancers are aggressive and overtreatment can lead to unnecessary side effects, such as hormone imbalances, bowel function issues and erectile dysfunction. After initial treatment, prostate cancer patients are often monitored with a prostate specific antigen (PSA) blood test, but this test provides no information about the location and the extent of the disease. Even with traditional bone scans and CT scans, remnant traces of the disease are difficult to find and often go undetected.
A few years ago, a new, more sensitive type of imaging technique had shown promise in early clinical studies abroad and Dr. Glenn Bauman, Radiation Oncologist at the London Health Sciences Centre, wanted to bring this technique into his practice. He recognized the potential benefits of this method, but didn’t realize how much it could impact the lives of his patients.
Bringing advances to local patients
The new technique, which was originally developed at the John Hopkins Hospital in Baltimore, consisted of a chemical probe, called [18-F]-DCFPyL, which would attach only to prostate cancer cells and light up in positron emission tomography (PET) scans. It can detect very small traces of a tumour that has returned after treatment or spread to a different part of the body.
Bauman teamed up with the co-inventor of [18-F]-DCFPyL, Dr. Martin Pomper, and the Centre for Probe Development and Commercialization (CPDC) to bring this probe to patients in Ontario. CPDC implemented the stringent manufacturing processes needed to create this probe and in March of 2016, Lawson’s researchers were the first to use this technique to scan a patient at St. Joseph’s Hospital in London.
“We teamed up with experts in [18-F]-DCFPyL from the U.S. and experts in prostate PET/CT from Australia to adopt this new technique, benchmark our methods and learn from their experience,” says Bauman. “It’s with collaborations like these that we can accelerate the implementation of new methods to help patients in Ontario.”
Evaluating the benefits for those with prostate cancer
Clinical studies are needed to evaluate the effectiveness new medical techniques in practice. For this technique, Bauman and collaborators needed to test whether it’s improved accuracy and sensitivity could help make better treatment decisions.
“Treatment plans for prostate cancer differ depending on the cancer’s size and location. Whether a cancer returns in the prostate, the pelvic area or elsewhere makes a big difference,” says Bauman. “We needed to test if more sensitive imaging techniques could help patients make better treatment decisions.”
Bauman led the design and development of the Advanced Prostate Imaging of Recurrent Cancer After Radiotherapy (PICs) study to evaluate [18-F]-DCFPyL PET/CT imaging. With OICR’s support over the following two years, PICs enrolled 80 men and scanned them with both traditional imaging methods and with [18-F]-DCFPyL PET/CT.
The study group found that not only can [18-F]-DCFPyL PET/CT detect smaller traces of the disease earlier when it is more manageable, this technique changed treatment recommendations for two in every five patients.
“With this technique, we were able to clarify and reclassify a lot of the traditional scans that were previously uncertain,” says Bauman. “This means that we were able to give prostate-directed treatment with confidence for patients whose cancers reemerged in their prostate and avoid the negative side effects of systemic hormone therapy for these patients.”
Bauman says that the technique also detected double the number of cancers outside of the prostate which were too small to be detected using traditional imaging alone.
Translating clinical findings into practice
Just three years after the first [18-F]-DCFPyL PET/CT scan was taken in Canada, Bauman has embarked on the next stage in translating these findings into routine practice. He and collaborators have teamed up with Cancer Care Ontario to provide access to the [18-F]-DCFPyL PET/CT technique in Toronto, London, Hamilton, Ottawa and Thunder Bay as part of a provincial registry program.
[18-F]-DCFPyL PET/CT can be applied to other challenges that patients and clinicans face with managing prostate cancer, including monitoring how patients respond to treatments. Notably, investigators in Hamilton are investigating how these scans can help predict a patient’s response to treatment in the OICR-supported MISTR trial.
“We have been sufficiently encouraged by our results from the PICs study, through which we have demonstrated the value of this intervention and how it can benefit men with prostate cancer,” says Bauman. “I’m proud to help bring better technologies to our patients in need and enable the adoption of these technologies throughout the province.”
May 10, 2019
Researchers look beyond an obvious hypothesis to connect patterns in gene expression with genome rearrangements, drawing attention to often-overlooked regions of the genome
If two different genes come together, the resulting gene fusion can have a new function that can cause or contribute to cancer. The discovery of cancer-causing gene fusions has led to the development of new therapies for many cancer types and sparked efforts to identify rearrangements that might yield new treatment targets. Often, however, researchers discover fusions with no effect on a cell, but a recent study has shown that the regions around these ‘fusions of unknown significance’ may be just as important to study as the fusion itself.
In their investigation into high grade serous ovarian cancer (HGSOC) – which has a five-year survival rate of only 20 per cent – the Genomics Program at OICR identified thousands of gene fusions and investigated the regions around these key points. As described in Scientific Reports, they found that the neighbouring regions are overexpressed – in essence, overactive – which may contribute to the cancerous nature of cells.
“Often, we find evidence of rearranged DNA without a clear picture of how rearrangements drive cancer,” says Dr. Paul Krzyzanowski, Director of Genome Technology Translation at OICR and primary author of the publication. “In this study, we found that the regions around gene fusions – in addition to the fusions themselves – are very active in cancer cells. This observation hints at the idea that we can look at broader genetic regions, and not just the location of a fusion by itself, to better understand how genomic rearrangements wreak havoc in cancer cells.”
In this study, we found that the regions around gene fusions – in addition to the fusions themselves – are very active in cancer cells
The observed overexpression of regions around fusions could be used to differentiate diseased cells from normal cells and lead to new cancer treatment approaches. The observations in this study are consistent with findings from the Pan-Cancer Analysis of Whole Genomes network, which identified patterns of overexpression in disturbed genomic regions across many cancer types.
Krzyzanowski says this work highlights a non-intuitive analytical approach for analyzing cancer-related gene fusions which will continue to be employed as OICR’s Ovarian Cancer Translational Research Initiative investigates how DNA rearrangements in ovarian cells drive cancer.
Read more about OICR’s Ovarian Cancer Translational Research Initiative or learn more about Genomics at OICR.
May 1, 2019
Study identifies earliest traces of brain cancer long before the disease becomes symptomatic
Toronto (May 1, 2019) – Brain tumours are the leading cause of non-accidental death in children in Canada, but little is known about when these tumours form or how they develop. Researchers have recently identified the cells that are thought to give rise to certain brain tumours in children and discovered that these cells first appear in the embryonic stage of a mammal’s development – far earlier than they had expected.
“Progress in the development of more effective brain cancer treatments has been hampered in large part by the complex heterogeneity – or the variety of cells – within each tumour,” says Dr. Michael Taylor, Paediatric Neurosurgeon and Senior Scientist in Developmental and Stem Cell Biology at The Hospital for Sick Children (SickKids) and co-lead of the study. “We recognized that new technologies could allow us to unravel some of this complexity, so we combined our expertise with McGill and OICR to approach this problem together.”
Using mouse models, the research group investigated the different types of normal brain cells and how they developed at various timepoints in the cerebellum of the brain – the most common location for childhood brain tumours to appear. They mapped the lineages of over 30 types of cells and identified normal cells that would later transform into cancerous cells, also known as the cells of origin.
To pinpoint these specific cells, the group relied on single cell sequencing technology, which allows researchers to look at individual cells more clearly than traditional sequencing methods.
In their investigation, the cells of origin were observed much earlier in fetal development than one would expect, says Taylor, who is also a Professor in the Departments of Surgery and Laboratory Medicine and Pathology at the University of Toronto and Co-lead of OICR’s Brain Cancer Translational Research Initiative.
“Our data show that in some cases, these tumours arise from cell populations and events that would occur in humans at six weeks in utero,” says Dr. Lincoln Stein, Head of Adaptive Oncology at OICR and co-lead of the study. “This means that the brain tumours may be starting long before they show in clinic, even before a woman may know she is pregnant.”
“The brain is extraordinarily complex. These findings are not only important for better understanding brain tumours but they will also allow us to learn more about these cells and how they work, in order to help children with neurodevelopmental delays. What we have accomplished as a team in this study brings hope for patients,” adds Dr. Nada Jabado, Paediatric Hemato-Oncologist and Senior Scientist in the Child Health and Human Development Program at the Research Institute of the McGill University Health Centre and co-lead of the study. Dr. Jabado is also a professor of Pediatrics and Human genetics at McGill University.
“If we can understand where these tumours originate, we can better understand which cells to target and when to target them to create more effective and less toxic therapies for children,” says Ibrahim El-Hamamy, PhD candidate at OICR and co-first author of the study. “We’ve found new avenues and opportunities in a very complex disease and we look forward to actualizing this potential.”
With this knowledge, researchers can now study the differences between the development of normal, healthy cells and the cells that will eventually give rise to cancerous cells.Continue reading – The unanticipated early origins of childhood brain cancer
April 25, 2019
It’s DNA Day! In this video, Prisni Rath, a Bioinformatician at OICR, explains what interests her about DNA and the importance of DNA to her work in clinical diagnostic research.
“I like that DNA has a direction.” Savo Lazic is a Scientific Associate in OICR’s Genomics Program. In this quick video he shares his favourite things about DNA and how new technologies are changing how researchers work with DNA.
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.”