April 7, 2021
Dr. Elizabeth Eisenhauer has been named the winner of the 2021 Canada Gairdner Wightman Award. The award is given to a Canadian scientist recognized for outstanding leadership in medicine and medical science throughout their career. Eisenhauer is receiving the award for her transformational research in cancer clinical trials and cancer drug delivery and the impact of her work for patients around the world.
Eisenhauer is Professor Emerita, Departments of Oncology and Medicine, Adjunct Professor of Oncology, Queen’s University and Innovation Lead, Kingston Health Sciences Centre. She is a current member of OICR’s Therapeutics Pipeline Advisory Committee, past Co-chair of OICR’s Scientific Advisory Board and was a founding member of OICR’s Board of Directors.
Eisenhauer has made fundamental contributions to the clinical evaluation of new cancer therapies, research strategy and clinical trials development that have been essential in the development of new treatments for ovarian cancer, malignant melanoma and brain tumours.
OICR congratulates Eisenhauer on this very well-deserved honour and thanks her for her past and current contributions to OICR and leadership in the cancer research community.
March 18, 2021
Gallinger brings more than three decades of clinical and interdisciplinary research experience to OICR leadership
Dr. Steven Gallinger has joined OICR’s executive leadership team as Head, Clinical Translation. In this role, he will lead one of OICR’s three key priority areas, Clinical Translation, which focuses on advancing Ontario cancer discoveries through early clinical validation, partnering with industry and the health system for downstream development and implementation.
Gallinger has more than three decades of experience as a surgical oncologist specializing in hepato-pancreatico-biliary surgeries. He is internationally recognized for establishing one of the largest population-based colon cancer registries, and he is well-known for his pancreatic cancer research, through which he has made significant contributions to large-scale genomics studies like the International Cancer Genome Consortium. Gallinger is passionate about building large biospecimens and data repositories to enable research discoveries.
In conjunction with Gallinger’s appointment, OICR is also proud to announce Dr. Glenn Bauman will continue as a Clinical Lead for Clinical Translation. Bauman, who has led several OICR research initiatives and clinical trials over the last 10 years, is a Radiation Oncologist at the London Health Sciences Centre who focuses on genitourinary and central nervous system tumours.
“The entire OICR executive is thrilled to have Dr. Gallinger join our leadership team,” says Dr. Laszlo Radvanyi, President and Scientific Director, OICR. “Steven’s deep experience as both a clinician and researcher will help OICR strengthen our bridge between the lab and the clinic. The continued contributions of Dr. Bauman will further accelerate our efforts to get novel solutions to patients in Ontario and around the world.”
“Translating research findings to improve clinical care is complex,” says Dr. Christine Williams, Deputy Director, OICR. “Success depends on the engagement of many partners, including the health system, health regulators and in some cases the private sector, as well as scientists, clinicians and especially patients and their families. Drs. Gallinger and Bauman are leaders in forging these partnerships and translating research into practice. We’re proud to welcome Dr. Gallinger to OICR’s executive team and delighted that OICR will continue to benefit from Dr. Bauman’s scientific leadership.”
Among his many career accomplishments, Gallinger and the multidisciplinary team at Princess Margaret has been the driving force behind the COMPASS clinical trial, which has led to seminal discoveries that are paving the way for new personalized pancreatic cancer therapies. As Head of Clinical Translation, Gallinger will continue co-leading the pancreatic cancer PanCuRx Translational Research Initiative and build upon PanCuRx’s translational achievements.
“This is an exciting time at OICR,” says Gallinger. “We’re looking to build on our existing networks and research successes. As we embark upon our new Strategic Plan, I think we can reach out and support research across more cancer centres so that we can work together to benefit patients sooner, while keeping Ontario at the forefront of precision cancer medicine.”
As part of her Deputy Director role, Williams will continue to oversee the Clinical Translation networks of the Clinical Translation portfolio, including the Canadian Cancer Clinical Trials Network, the Ontario Cancer Research Ethics Board and the Ontario Health Study.
March 4, 2021
The Canadian Cancer Trials Group (CCTG), based in Kingston, Ont., will lead a new initiative called ExCELLirate Canada that will develop and optimize distributed point-of-care manufacturing that will improve efficiency, quality, and capacity to test innovative “made in Canada” cell therapies. Canada’s Minister of Innovation, Science and Industry, François-Philippe Champagne, today announced $5.1 million in funding through the Canadian Foundation for Innovation to launch the platform.
ExCELLirate Canada will help researchers bring new therapies to market and ultimately provide better outcomes for Canadians with cancer. Many patients do not survive the month required to produce CAR T- cells using the current system. Through ExCELLirate Canada, Canadians will have rapid access to innovative cell therapies. OICR is a partner in the initiative along with other leading research organizations across Ontario and Canada.
“ExCELLirate will allow Canada to shift our efforts in cell therapy into high gear and be at the forefront of this game-changing technology while providing patients more access to this cutting-edge therapy,” says Dr. Laszlo Radvanyi, President and Scientific Director of OICR. “I congratulate our friends at CCTG and the ExCELLirate team on the funding announced today. We at OICR are so proud to be part of this important work.”
February 26, 2021
An OICR-supported research team at the Princess Margaret Cancer Centre has shown that adding a targeted drug to chemotherapy results in longer survival and a stronger response to treatment in a difficult-to-treat form of ovarian cancer.
When a patient’s ovarian cancer becomes resistant to treatment, the patient has few alternative options and faces an estimated survival of less than 18 months. This is a reality for approximately one in four women with the disease.
Against this challenge, a team OICR-supported through OICR’s Ovarian Cancer Translational Research Initiative (TRI), headed by Dr. Stephanie Lheureux, Princess Margaret (PM) Clinician Investigator and Dr. Amit Oza, PM Senior Scientist and OICR TRI leader, led a Phase II clinical trial including nearly 100 women across 11 centres to evaluate the combination therapy of adavosterib and gemcitabine. Their discoveries, which were recently published in The Lancet, demonstrated that this combination increased survival by 4.3 months relative to chemotherapy and placebo alone. 23 per cent of patients’ cancers responded to the chemotherapy, in contrast to a 6 per cent response rate seen using chemotherapy alone.
“By combing two drugs, we were able to change the trajectory of cancer for a high-risk group of women with advanced disease who did not have many choices left,” says Oza, Medical Director of the Cancer Clinical Research Unit and Co-Director of the Bras Drug Development Program at Princess Margaret Cancer Centre. “That is significant.”
Lead author Dr. Stephanie Lheureux says that the study provides a signal of hope for women with ovarian cancer who develop drug-resistance to treatment. The study included some women who had received up to eight different previous treatments which had stopped working.
“As we learn more and more about the biology of tumours, we can target treatments more precisely to the molecular changes in a cancer to improve the type and response of our treatments. That will change outcomes for patients,” says Lheureux, who is also the Princess Margaret Site Lead for Gynecological Oncology. “I want our patients to know there is hope to find better treatment to control their cancer.”
By combing two drugs, we were able to change the trajectory of cancer for a high-risk group of women with advanced disease who did not have many choices leftDr. Amit Oza
The study participants had high-grade serous ovarian cancer – the most malignant form of ovarian cancer, accounting for up to 70 per cent of all ovarian cancer cases. They were randomly assigned to receive either adavosertib plus gemcitabine (chemotherapy) or placebo plus gemcitabine.
The patients’ tumours were biopsied before and during treatment to assess the effectiveness of the drug regimens. Analysis of genetic mutations and changes in DNA damage response pathways was performed by the Joint Genomics Program at OICR and the Princess Margaret Cancer Centre.
“This discovery underscores the importance of bringing scientists and clinicians together to tackle difficult questions from different perspectives to offer new insights into the biology of cancer,” says Dr. Laszlo Radvanyi, President and Scientific Director, Ontario Institute for Cancer Research. “It shows how we can push these damaged cancer cells right smack into mitotic catastrophe to their demise. This clinical trial has validated good science that has begun to uncover how a cancer cell’s own DNA repair mechanism can be used against it and capitalizes on this unique vulnerability by combining drugs in a smart way. The small-molecule DNA repair inhibitors used in this study targeting the G2-M checkpoint hold great promise as chemotherapy enhancers by further damaging and ultimately destroying tumour cells, thereby overcoming treatment-resistant ovarian cancer.”
In addition to improving overall survival by 4.3 months, the combination of adavosertib and gemcitabine improved progression-free survival by 1.6 months relative to chemotherapy alone.
“Taken together, these three outcomes give us a strong signal that we can potentially improve survival for these patients who face bleak prospects,” says Dr. Oza, adding that the study carefully co-ordinated patients with similar genomic backgrounds with a targeted drug that exploits a defect in cancer cells.
“This is precision medicine at its best,” he adds. “This is how we will develop better treatments for our patients.”
Through whole-exome sequencing, the study found that patients’ tumours acquire several changes – or mutations – that play an important role in regulating critical cell cycle checkpoints. These mutations could disable these “quality control” checks, allowing cancer cells with damaged DNA to continue dividing and growing unimpeded.
Further, they discovered that the drug adavosertib could effectively target tumour cells that harbour the key TP53 mutation.
“We exploited a fatal flaw in cell division, diverting and stopping the damaged cells from growing into a tumour,” explains Lheureux. “We showed the potential of targeting the cell cycle in a specific subgroup of patients with highly resistant ovarian cancer. This opens up new avenues of treatment possibilities.”
The research group now plans to evaluate the impact of this combination on patients’ quality of life and analyze patients’ blood samples to search for blood-based indicators of treatment resistance.
In addition to OICR’s support, the study was also funded by the Princess Margaret Cancer Foundation, the U.S. National Cancer Institute Cancer Therapy Evaluation Program, the U.S. Department of Defense Ovarian Cancer Research Program, and AstraZeneca.
February 19, 2021
Inhibiting a key enzyme could help stop the growth of glioblastoma
Fewer than 10 per cent of people diagnosed with glioblastoma will survive beyond five years. Despite advances in understanding this deadly brain cancer, therapy options for this disease are severely limited. In a study recently published in Nature Communications, researchers have discovered that inhibiting a key enzyme, PRMT5, can suppress the growth of glioblastoma cells. Their findings demonstrate a novel approach to treating the disease, paving the way for a new class of therapeutics.
A multidisciplinary team with expertise in cancer stem cells, protein structures, small molecule development and multi-omic analyses enabled this discovery. The group, was co-led by Dr. Peter Dirks, Senior Scientist and Neurosurgeon at the Hospital for Sick Children (SickKids) and co-leader of OICR’s Brain Cancer Translational Research Initiative along with researchers at the Princess Margaret Cancer Centre, the Structural Genomics Consortium (SGC) and the University of Toronto. Many of the researchers involved in the study are also part of the Stand Up To Cancer (SU2C) Canada Cancer Stem Cell Dream Team, which receives support from OICR.
Through the study, they showed that inhibiting PRMT5 affected a large network of proteins that are important in cell division and growth, triggering cell senescence, and stopping the unrelenting division of cancer cells.
While PRMT5 inhibition has been previously suggested as a way to target brain and other cancers, no one has tested this strategy in a large cohort of patient tumour-derived cells that have stem cell characteristics, cells that are at the roots of glioblastoma growth.
They found that specific molecules – precursors to actual therapeutic drugs – inhibited the same enzyme, PRMT5, stopping the growth of a large portion of these patient-derived cancer stem cells. Many current drugs do not eliminate cancer stem cells, which may be why many cancers regrow after treatment.
“We used a different strategy to stop cancer cells from proliferating and seeding new tumours,” says co-senior author, Dr. Cheryl Arrowsmith, Senior Scientist at the Princess Margaret Cancer Centre who leads the University of Toronto site of the SGC. “By inhibiting one protein, PRMT5, we were able to affect a cascade of proteins involved in cell division and growth. The traditional way of stopping cell division has been to block one protein. This gives us a new premise for future development of novel, more precise therapies.”
“This strategy also has the opportunity to overcome the genetic variability seen in these tumours,” says co-senior author, Dirks, who also leads the SU2C Canada Dream Team. “By targeting processes involved in every patient tumour, which are also essential for the tumour stem cell survival, we side-step the challenges of individual patient tumour variability to finding potentially more broadly applicable therapies.”
The researchers also examined the molecular features of the patient-derived glioblastoma cells by comparing those that responded well to those that did not respond as well. They found a different molecular signature for the tumour cells that responded. In the future, this could lead to specific tumour biomarkers, which could help in identifying those patients who will respond best to this new class of drugs.
The research group will continue testing PRMT5 inhibitors to develop new therapies for people with glioblastoma.
“Right now, we have too few medicines to choose from to make precision medicine a reality for many patients,” says Arrowsmith. “We need basic research to better understand the mechanism of action of drugs, particularly in the context of patient samples. This is what will help us develop the right drugs to give to the right patients to treat their specific tumours.”
The research group also included OICR-affiliated scientists and staff researchers, Drs. Trevor Pugh, Mathieu Lupien, Benjamin Haibe-Kains, and Ahmed Aman.
Adapted from a SickKids news release.
February 4, 2021
Phase III clinical trial of men with a clinical suspicion of prostate cancer finds MRI with targeted biopsies to be more accurate at diagnosis and less intrusive than current standard
Toronto – (February 4, 2021) The results of a Phase III randomized clinical trial have shown that when it comes to detecting clinically significant prostate cancer, Magnetic Resonance Imaging (MRI) with targeted biopsies (MRI-TBx) matches the current standard and brings a multitude of advantages. The PRostate Evaluation for Clinically Important Disease: MRI vs Standard Evaluation Procedures (PRECISE)study will help to make prostate cancer diagnosis more accurate and less invasive.
PRECISE included 453 participants at Canadian academic cancer centres who were either assigned to receive MRI imaging followed by MRI-TBx of suspicious areas (identified by MRI), or the current standard of care of a systematic 12-core transrectal ultrasound-guided (TRUS) biopsy (TRUS-Bx).
- MRI with targeted biopsy found five per cent more clinically significant prostate cancers compared to those receiving systematic TRUS-Bx biopsies, conclusively demonstrating the method can at least match the performance of the current standard of care.
- Compared to standard TRUS-Bx, the MRI-TBx were found to be better in identifying clinically significant cancers.
- More than a third of patients in the MRI arm of the trial avoided biopsies altogether following negative imaging results. Those individuals received a follow-up MRI in two years’ time.
- Those who did have biopsies in the MRI arm had significantly fewer samples taken when compared to systematic TRUS-Bx, resulting in less pain and discomfort for patients. Moreover, the MRI arm had a decreased adverse event profile, including less hematuria (blood in the urine) and incontinence.
- There is a major unmet need for a test that identifies clinically significant prostate cancer while avoiding overdiagnosing clinically insignificant cancers. Use of MRI reduced the unnecessary diagnosis of slow growing, clinically insignificant prostate cancers by 55 per cent.
These findings show decisively that MRI together with targeted biopsies offer patients a less invasive procedure, the chance to avoid a biopsy all together and can help avoid the over-treatment of clinically insignificant prostate cancer – all while detecting a higher rate of clinically significant cancers.
“My colleagues and I are thrilled about these results that show, without a doubt, that imaging and targeted biopsies are the future of prostate cancer diagnosis. We can catch more of the cancers we should be treating, avoid unnecessary treatment at the same time and improve the quality of life for our patients.” says Dr. Laurence Klotz, Chair of Prostate Cancer Research at Sunnybrook Health Sciences Centre and lead author of the study. “We thank the study participants and our funders for their support and look forward to continuing our efforts to have this technology used more widely.”
“The study’s findings have influenced Ontario Health-Cancer Care Ontario’s upcoming, updated Prostate MRI Guidelines, which will be released this year,” says Dr. Masoom Haider, co-lead of the study and Professor of Medical Imaging at the University of Toronto, and Clinician Scientist with the Ontario Institute for Cancer Research (OICR). “I am pleased to see our research produce results that will make a real difference in how prostate cancer is diagnosed and improve the lives of patients.”
“I congratulate Dr. Klotz and the PRECISE team on this truly impactful research which will change clinical care and make a difference for men with prostate cancer,” says Dr. Christine Williams, Deputy Director and Head, Clinical Translation, OICR. “It is a great example of how, with our partners, we are moving research innovations to the clinic to improve the lives of patients and treat cancer with improved precision.”
“These practice-changing results will have a significant and positive impact on the roughly 64 Canadians who are diagnosed with prostate cancer every day. Thanks to the efforts of Dr. Klotz and his team, people will need to undergo fewer biopsies and for some of them, they will be spared from unnecessary biopsies and treatments altogether,” says Dr. Stuart Edmonds, Executive Vice President, Mission, Research and Advocacy at the Canadian Cancer Society. “We are proud to support this research, which will help people with prostate cancer live longer, fuller lives.”
“At Movember, we are honoured to play a role in funding cutting-edge research like the PRECISE study, ultimately helping to provide more positive outcomes for men living with or beyond a prostate cancer diagnosis,” says Todd Minerson, Country Director for Movember Canada.
PRECISE was funded by the Canadian Cancer Society with funds provided by Movember and by the Ontario Institute for Cancer Research.
About the Ontario Institute for Cancer Research
OICR is a collaborative, not-for-profit research institute funded by the Government of Ontario. We conduct and enable high-impact translational cancer research to accelerate the development of discoveries for patients around the world while maximizing the economic benefit of this research for the people of Ontario. For more information visit http://www.oicr.on.ca.
About the Canadian Cancer Society
The Canadian Cancer Society (CCS) is the only national charity that supports Canadians with all cancers in communities across the country. No other organization does what we do; we are the voice for Canadians who care about cancer. We fund groundbreaking research, provide a support system for all those affected by cancer and shape health policies to prevent cancer and support those living with the disease.
Help us make a difference. Call 1-888-939-3333 or visit cancer.ca today.
Movember is the leading charity changing the face of men’s health on a global scale, focusing on mental health and suicide prevention, prostate cancer and testicular cancer. The charity raises funds to deliver innovative, breakthrough research and support programs that enable men to live happier, healthier and longer lives. Committed to disrupting the status quo, millions have joined the movement, helping fund over 1,250 projects around the world. In addition to tackling key health issues faced by men, Movember is working to encourage men to stay healthy in all areas of their life, with a focus on men staying socially connected, and becoming more open to discussing their health and significant moments in their lives. The charity’s vision is to have an everlasting impact on the face of men’s health. To donate or learn more, please visit Movember.com.
February 3, 2021
How OICR is using strategic foresight to prepare for the future and inform its 2021-2026 Strategic Plan
OICR focuses on translating cancer research discoveries and transforming cancer care. Achieving this mission, however, is dependent on a myriad of factors beyond scientific research and development. Social, political, technological, economic and environmental factors all may play a role in driving the future of cancer research and care in Ontario and beyond.
As part of the process to develop its 2021-2026 Strategic Plan, OICR partnered with Dr. Peter Bishop, Professor Emeritus at the University of Houston, professional futurist and President of Strategic Foresight and Development, to investigate the possible futures of cancer research and care in Ontario and around the world. OICR plans to launch the 2021-2026 Strategic Plan in April 2021.
With the help of leaders from research institutes, hospitals and the public sector across Ontario, 20 key drivers were identified that may significantly affect the future of cancer, including an aging population, innovations in quantum computing and the growing focus on holistic health. The group then designed and evaluated potential future scenarios and derived four main insights that were used to inform OICR’s 2021-2026 Strategic Plan:
While health-related datasets continue to grow and new sources of data emerge, standards around data gathering, monitoring, integration, sharing and implementation remain unclear. These parameters affect how the cancer community implements precision medicine for people living with cancer. Through its 2021-2026 Strategic Plan, OICR’s computational biology and informatics research programs will continue to develop essential data tools and apply responsible data sharing standards, while strengthening Ontario’s global leadership in health data integration and federation through initiatives such as the Global Alliance for Genomics and Health, the International Cancer Genomics Consortium Accelerating Research in Genomic Oncology, Canada’s Digital Health and Discovery Platform, and the Ontario Data Integration Network.
Integrating the perspectives of patients into research is becoming increasingly important to ensure that research ultimately leads to patient benefit. Over the next few decades, patients will increasingly have access to more information and misinformation, challenging the research and health communities to ensure patients receive the information they need to make informed decisions. To address these challenges, OICR will foster and grow meaningful partnerships with patients and caregivers to integrate patient values into OICR priorities. OICR is currently developing a Patient Family Advisory Council, which will advise on OICR’s patient partnership initiatives.
As the cost and urgency of cancer drug development continue to increase, alternative funding for research and translation may become necessary. This challenge has become more apparent as the world looks to recover from the socio-economic impacts of the coronavirus pandemic. OICR will continue to strengthen partnerships within the cancer ecosystem over the next five years, to attract further investment in cancer research and innovation to Ontario. OICR will also build health services research expertise into critical research programs to evaluate the costs and benefits of emerging interventions to support the path between discovery and patient care.
Trust between stakeholders in the cancer system – including patients, families, researchers and clinicians – is critical to progress in cancer research. Trust is imperative to data gathering, sharing and processing, and these data are necessary to make cancer detection and treatment more precise. Through the 2021-2026 Strategic Plan, OICR aims to work together with partners to ensure we remain and become an even more trusted custodian of patient data and scientific information to support high quality translational research, bridging the lab to the clinic.
“Our mission is based on translating cancer research discoveries to transform cancer care,” says Dr. Rebecca Tamarchak, Senior Director of Strategic Planning and Governance. “Integrating foresight into our strategic planning process is our way to proactively anticipate the future in order to develop a nimbler strategy.”
The strategic foresight workshop, which was hosted in late 2018, kicked off OICR’s multi-phase strategic planning process. The process, led by Tamarchak and OICR’s President and Scientific Director, Dr. Laszlo Radvanyi, has incorporated insights from extensive consultations with OICR staff, collaborators and the community.
“This strategic foresight study has reinforced the importance of enduring partnerships across the cancer research community and we look forward to strengthening those relationships over the next five years to maximize our impact on cancer patients and the Ontario economy,” says Tamarchak. “We’re excited to bring the 2021-2026 Strategic Plan into action.”
January 8, 2021
Q&A with new OICR Investigator Dr. Shraddha Pai on uncovering the hidden differences between cancers
OICR is proud to welcome Dr. Shraddha Pai to its Computational Biology Program as a Principal Investigator. Here, Pai discusses current challenges in understanding diseases and what motivates her to tackle some of the biggest challenges in biomedical research.
What are some of the research questions you’re interested in?
I’m very driven to understand why different people with the same cancer type, have different outcomes and respond differently to the same treatment. As genomic assays get cheaper, we learn more about molecular interplay in different cells, and our population datasets become larger and mature, we are able to integrate different layers of the genome and cell types, to try to get at this question. For example, we now believe there are four main types of medulloblastoma with different underlying molecular networks and outcomes. This field of research is called ‘precision medicine’: using patient profiles to match them with the most effective treatment. But really this is just a new phrase to describe what doctors have been doing since the dawn of medicine; it just means that now we’re using powerful computers and algorithms to find patterns in much larger and complex genomic datasets. The principle is the same.
As a trainee in Dr. Gary Bader’s group, I led the development of an algorithm that integrates several types of patient data to classify patients by outcome. Our method – called netDx – adapts the idea of recommender systems, used by Netflix and Amazon, to precision medicine. Just as one would ask Netflix to “find movies like this one”, netDx helps identify patients “with a treatment profile like this”. In a benchmark, netDx out-performed most other methods in predicting binary survival in four different types of cancer. Importantly, netDx is interpretable, and recognizes biological concepts like pathways. This makes it a useful tool to get mechanistic insight into why a predictor is doing well, and provides a way to understand the underlying biology and perhaps drive rational drug design.
I also have a special interest in understanding the link between epigenetics and disease, particularly as this pertains to the brain. Epigenetics refer to molecular changes that change how the genome behaves – for example, turning a gene on or off in a given cell type. My own previous research in mental illness has found epigenetic biomarkers related to psychosis, which explain the distinctive features of this condition. The same may be the case in certain types of cancers, particularly those of developmental origin.
How do you plan to unravel these complex layers of biology?
My research program has two main goals. The first is to build models for precision medicine – predicting disease risk, treatment response – starting with population-scale datasets that have several types of patient data. I’m hoping to use existing and emerging data such as UK BioBank, CanPath, ICGC-ARGO and the Terry Fox Research Institutes’ datasets, and ongoing clinical trials, to identify which clinical outcomes are easily amenable to our approaches. The models my group builds will incorporate prior knowledge about genome organization and regulation, so that these are interpretable. For example, we will use epigenomic maps of specific tissue types, or data from single-cell resolution maps, pathway information, to find and organize relevant needles in the genomic haystack. This feature will give us interpretability, which is key to increasing confidence in a model, as well as to improving the understanding of cellular pathways that affect disease and eventual drug development.
My second goal is to understand the epigenomic contributions – particularly developmental changes – to cancer risk, using a combination of molecular biological, genomic and analytic techniques.
As I work toward these goals, I hope to collaborate on complementary projects, such as identifying DNA methylation changes in circulating tumour DNA and improving how we subtype adult tumours. These projects will hopefully lead to new biomarkers, and ultimately improvements to how we diagnose and treat cancer.
Importantly, the software that my team builds will also be openly available to the research community, so others can apply my methods to different types of diseases. I’m excited to get started.
Your work applies beyond cancer. How do you traverse these different disease areas?
The reclassification of disease based on molecular or other biomarkers, and how disease subtype affects risk and treatment response, isn’t unique to cancer – the same research questions extend to other types of disease such as metabolic diseases, autoimmune diseases and mental illness. At the end of the day, we are looking at the same system organized at the molecular, cellular and organ-level, with similar principles of genomic regulation and perhaps similar considerations for drug discovery. Our algorithms are based on these general principles and can therefore be used to answer similar questions for different disease applications, or very different types of cancer. Of course, it’s important to collaborate with teams that have domain expertise to make sure the algorithms are “fine-tuned” for a particular application, and I look forward to benefitting from those partnerships.
What excites you about this type of work?
I’m excited to join a community where basic research is so strongly connected to clinical purpose. Personally, I am very motivated by the prospect of a positive impact on patients within my lifetime and feel that my group’s work is more likely to have a valuable impact in an environment that combines basic and translational research. That said, we’re only just beginning to see the benefits of precision medicine and many challenges remain to bring genomic knowledge into practice. I hope that I can create more useful methods and models for precision medicine and improved clinical decision-making in the coming decade.
I’m especially excited to be at OICR because of the Institute’s access to clinical trials, strong genomics and computational biology program, and pharmacology team. If my group can find promising biomarkers and leads, we can work with OICR collaborators in the Genomics and Drug Discovery groups to move from basic research to application.
December 9, 2020
The tool can accurately distinguish real mutations from sequencing mistakes to improve the early detection of cancer
DNA mutations in cancer cells are caused by different processes, each of which leaves a genetic fingerprint that can provide clues to how the cancer develops. Researchers have now applied this understanding to reduce errors when reading DNA, allowing them to accurately and efficiently detect the smallest traces of mutated cells in the blood.
In a recent publication in Science Advances, an OICR-supported research group outlines a new and improved statistical model to reduce error rates in DNA sequencing data. They demonstrate that their model, called Espresso, outperforms current error suppression methods.
“When we isolate, amplify and try to read the individual building blocks of DNA, we encounter a lot of errors,” says Dr. Sagi Abelson, OICR Investigator, Assistant Professor at the University of Toronto and first author of the publication. “This is a major obstacle. The high error background makes it difficult to pinpoint authentic rare mutations. This is what Espresso aims to solve.”
To build an effective error-suppressing statistical model, the group assessed the different types of errors in their relative genomic contexts across more than 1,000 sequencing samples. Their approach was based on assessing the genetic fingerprints within these samples and mapping them to the regions around the errors to understand if the error was a true mistake, or if it was an important mutation.
“The key advantage of our method is that it allows scientists to read DNA more accurately without the need to duplicate efforts using a set of independent control measurements to estimate error rates,” says Abelson. “This means that researchers can be more efficient with their time and resources. They can do more with less. We’re proud to have developed methods that can make research more practical and simple, but also more effective, efficient and accurate.”
This model is built on Abelson’s prior research published in Nature, which discovered early indicators of acute myeloid leukemia (AML) in the blood up to 10 years before symptoms surfaced. With Espresso, the research group was able to develop and test a new strategy to predict leukemia development, which could predict up to 30 per cent of AML cases years before clinical diagnosis with extremely high specificity. Importantly, this study demonstrated that the risk of developing AML can be measured by looking into only a small number of genomic bases, which suggests a more practical route to clinical testing and implementation.
“This work builds on our prior research, which has shown that we can detect AML earlier than thought possible,” says Dr. John Dick, Senior Scientist at the Princess Margaret Cancer Centre, Co-lead of OICR’s Acute Leukemia Translational Research Initiative and co-senior author of the study. “With these methods, we’ve now shown that we can focus in on specific areas of DNA to detect those early traces of AML with higher accuracy than ever before.”
“These methods are essential to advancing personalized cancer care in practice,” says Dr. Scott Bratman, Senior Scientist at the University Health Network’s Princess Margaret Cancer Centre and co-senior author of the study. “With these tools, we can enable clinicians to treat cancer more effectively, tailor treatment decisions and monitor minimal residual disease. We look forward to furthering our research for patients today and those who will develop cancer in the future.”
December 1, 2020
A national consortium including the Ontario Institute for Cancer Research will expand development of a software platform for genomics and health data and apply it to COVID-19. The $5.1 million project, called COVID Cloud, is co-funded by Canada’s Digital Technology Supercluster and aims to increase Canada’s capacity to harness exponentially growing volumes of genomics and biomedical data to advance precision health. The platform will be used by data scientists and domain experts to help understand, predict, and treat COVID-19 with molecular precision. With a global death count of over 1.4 million people and record numbers of cases nationally, solutions that can help Canada respond to ongoing challenges of the pandemic are urgently needed.
“We are proud to continue to support this consortium’s groundbreaking work through our COVID-19 program,” said Sue Paish, CEO of the Digital Technology Supercluster. “This project shows how Canadian partnerships across multiple organizations and sectors can drive innovation, help us address global health issues, showcase Canadian expertise, and position us well to rebuild and grow our economy.”
The project — a collaboration between BioSymetrics, Centre of Genomics and Policy at McGill University, DNAstack, FACIT, Genome BC, Mannin Research, McMaster University, Microsoft Canada, Ontario Genomics, Ontario Institute for Cancer Research, Roche Canada, Sunnybrook Research Institute, and Vector Institute — brings together Canadian leaders in software engineering, artificial intelligence, cloud computing, genomics, infectious disease, pharmaceuticals, commercialization, and policy. It leverages past work of partners to address needs of infectious disease research with guidance from domain experts.
“Tools that allow us to interrogate SARS-CoV-2 at a molecular level are essential to addressing this global health crisis, both now and in the future,” said Dr. Samira Mubareka, a microbiologist and infectious diseases physician at Sunnybrook, whose team was one of the first in Canada to isolate the novel coronavirus. “The insights we will learn by analysing integrated datasets using technology platforms like COVID Cloud can increase our preparedness for future waves and outbreaks.” Dr. Mubareka will co-chair the project’s translational science efforts along with Dr. Gabriel Musso, Chief Scientific Officer for BioSymetrics. “The infrastructure developed by this initiative will propel collaborative Canadian drug discovery efforts for COVID-19,” said Musso, whose team will lead bioinformatics and computational drug discovery for the project.
A major goal of the project is to make it easy for producers of genomic and health data to share data responsibly over industry standards, and for researchers to harness the collective power of information shared through them. The project deliverables include a suite of software products powered by enterprise-grade implementations of standards developed by Global Alliance for Genomics & Health (GA4GH), protocols that are being designed to facilitate the responsible sharing of genomic and health data, which will help advance precision medicine initiatives around the world.
“The platform is being built on a foundation of open standards that will allow for distributed networks of genomics and biomedical data to be built,” said Dr. Marc Fiume, CEO at DNAstack, whose team will lead software engineering for the project. “We are excited to see these technologies breaking down barriers to data sharing, access, and analysis and create new opportunities for genomics-based discoveries for our partners.”
This project is responding to global demand for highly specialized, scalable, distributed software infrastructure to support collaborative genomics research — a need that has surged since the onset of the COVID-19 pandemic. “COVID-19 has accelerated digital transformation of many industries, especially in healthcare,” said Kevin Peesker, President of Microsoft Canada. “The incredible power of Cloud applied to COVID at scale is expanding development of an information superhighway to securely connect scientists in Canada and around the world to the data and compute power they urgently need to help us overcome one of the greatest global health crises of our time.”
The platform will be used to support a series of projects in partnership with Canadian academic, clinical, and pharmaceutical collaborators, which are being coordinated by Canadian genome centres, Genome British Columbia and Ontario Genomics. These initial projects are being prioritized based on urgency and potential impact on Canada’s response to the COVID-19 pandemic.
“The COVID Cloud is an incredible platform that brings together resources and capacity to enable timely and comprehensive genomic analysis of SARS-CoV-2 for our province and our country,” said Bettina Hamelin, President and CEO of Ontario Genomics, whose team leads the ONCoV Genomics Coalition. “This made-in-Canada solution will immediately accelerate Canada’s response to COVID-19, while being a technological springboard for translating genomic data analysis into actionable medical insights across other disease areas in years to come.”
For more information, visit dnastack.com/solutions/covid-cloud.
November 24, 2020
As records are becoming more accessible and patients are becoming more engaged with their health data, who will make it all make sense?
Cancer patients are becoming increasingly involved with their care decisions and care systems are increasingly providing patients access to their test results, health data and relevant reports. These reports, however, can be dense, technical and confusing, leading to more questions than answers for patients and their caregivers. Dr. Nathan Perlis at the Princess Margaret Cancer Centre is dedicated to bridging this gap between patients and their health information.
“Traditional radiology and pathology reports were designed for a specific reason, to communicate results between experts in the field, from physician to physician,” says Perlis, Staff Urologist in the Department of Surgical Oncology at the Princess Margaret Cancer Centre and Assistant Professor at the University of Toronto. “We can’t expect that traditional forms will communicate information effectively with patients and caregivers. Our team recognized the need to design new documents to convey the most relevant information for patients in an easy-to-understand way.”
Perlis and collaborators – including OICR and Sinai Health’s Dr. Masoom Haider, UHN’s Healthcare Human Factors team and a group of patient partners – decided to address a key report used in making prostate cancer treatment decisions – the prostate magnetic resonance imaging (MRI) radiology report.
“Unlike a blood pressure measurement or a fever, prostate MRI results are difficult to interpret,” says Perlis. “This can cause unnecessary anxiety and confusion and barriers between patients and their care team. Our new patient-centred design addresses these concerns, providing a steppingstone for further discussion between patients and their clinicians.”
The team recently published their patient-centred radiology report design, coined PACERR, in the Canadian Urological Association Journal. Their design includes key elements including diagrams, a legend and a glossary to help make the MRI results more understandable. All elements of the form – including the format, layout and the language – were developed and evaluated in partnership with patients and caregivers. The group is now evaluating the form in a clinical trial.
In parallel, the group has recognized a key barrier to implementing these forms in practice. Creating these forms would significantly add to the reporting burden on radiologists. Perlis and collaborators have now set out to create a software package that can read a traditional standard report and automatically complete a tailored patient-centred report. As they develop this software, they hope to apply their learnings to other types of reports across different cancer types.
“Patient-centred communication tools are necessary for shared decision-making,” say Perlis. “We can imagine a future where patients are truly enabled and engaged in their health decisions and this work is a purposeful step toward that goal.”
This research was funded in part by OICR’s Investigator Awards Program.
November 13, 2020
Research team develops a Google maps-like algorithm to pinpoint when cancer patients may diverge from the standard course of treatment
Every cancer patient’s experience is unique but there are standard sequences of steps that help patients and their care teams navigate through screening, diagnosis, treatment and monitoring. These steps are published in pathway maps but are these maps followed in practice? Researchers supported by OICR’s Health Services Research Network, led by Drs. Timothy Chan and Claire Holloway, are working to answer that question.
Chan and collaborators at Ontario Health have developed new methods to measure the difference between a standard clinical pathway map and the actual care that a patient receives in practice. They leveraged real-world health data from Ontario patients to develop these methods, which could potentially be used to identify targets for quality-improvement initiatives.
“Pathway maps help optimize patient survival, healthcare costs and wait times at a population level,” says Holloway, co-principal investigator of the project and Provincial Clinical Lead of Disease Pathway Management (DPM) at Ontario Health.
“We have now derived a way to measure the alignment between actual care and the care described in a pathway map, analogous to measuring how a driver’s route differs from the Google Maps-suggested route,” says Chan, co-principal investigator of the project, Professor at the University of Toronto and Canada Research Chair in Novel Optimization and Analytics in Health.
To address this challenge, the team based their algorithm on an inverse optimization framework, a type of framework used to solve problems across a variety of disciplines, including telecommunications routing, medical radiation therapy planning, and investment portfolio management.
The research team first applied their methods to stage III colon cancer patient data and is now applying their methods to breast cancer care. The ultimate goal would be to use these methods across different cancer sites and potentially different diseases to help promote and implement best practices along the care continuum in Ontario’s healthcare system.
“We’re proud to apply our framework at a large scale to help provide meaningful quantitative measures of system efficiency and variation,” says Chan. “It’s exciting to see that these methods could allow Ontario Health to monitor and evaluate complex practice patterns at a population level.”
“Variations between a patient’s experience and the standard clinical pathway map isn’t necessarily a bad thing but it may prompt us to investigate further,” says Dr. Katharina Forster, Team Lead of DPM at Ontario Health. “We can look into why, when and where the variation is occurring. In this way these new methods and tools are allowing us to generate hypotheses about the causes of variation so we can better understand our care practices, make data-driven decisions and ultimately improve our cancer care system.”
“Ultimately, we’re looking to measure, monitor and improve our system across the province,” says Holloway. “Our rich data in Ontario and our capabilities in machine learning are outstanding. Thanks to OICR, we can bring these disciplines together to make a positive impact on our health system.”
The Health Services Research Network is co-funded by OICR and Cancer Care Ontario, now part of Ontario Health.