September 10, 2020
OICR-supported researcher Dr. Harriet Feilotter leads liquid biopsy research program
As the COVID-19 pandemic has impacted many areas of life, including the diagnosis and treatment of other health conditions, people have chosen to forgo cancer screening and care in attempt to minimize their potential exposure to the virus. Relative to the general population, people living with cancer are more susceptible to the virus, but delaying cancer treatment may allow the disease to grow or spread.
Dr. Harriet Feilotter has teamed up with members of the pan-Canadian Digital Technology Supercluster to bring greater access to cancer testing and treatment during the pandemic and beyond. Through the $2.59 million Project ACTT (Access to Cancer Testing & Treatment in Response to COVID-19), they aim to provide liquid biopsy solutions, which require only a simple blood draw, as alternatives to surgical tissue biopsies for cancer diagnosis and care.
“The goal is to allow patients alternatives to invasive procedures that may be difficult to access during a pandemic,” says Feilotter, Molecular Geneticist and Scientist at Kingston Health Sciences Centre, faculty member of Queen’s Cancer Research Institute and OICR Associate. “Not only would this benefit those patients who live far from large cancer centres, but it could limit patient exposure to COVID-19 and increase health system capacity.”
The collaborative team is led in part by Canexia Health, which develops specialized cancer genomic assays, and Patriot One Technologies Inc.’s subsidiary Xtract AI, which specializes in machine learning solutions across a variety of applications, among other private and public partners. Together, they will work to enhance their current tests that detect mutations in circulating tumour DNA (ctDNA) from blood and deploy these tests for multiple cancer types across Canada.
Now through ACTT, some patients have access to these tests in British Columbia, Ontario, Quebec and Saskatchewan. The long-term objective is to increase access across the country.
“The development of liquid biopsies and ctDNA testing has been accelerated by this pandemic,” says Feilotter. “We’re proud to team up in this cross-disciplinary, cross-sector collaboration to bring these promising solutions to more patients.”
September 3, 2020
OICR-based PhD Candidate awarded University of Toronto COVID-19 Student Engagement Award
When the COVID-19 pandemic shut down labs across Canada, cancer research trainees looked for ways to help respond to the pandemic. PhD candidates Tom Ouellette and Jim Shaw saw an opportunity to combine their skills and contribute to the cause.
Ouellette and Shaw were recently awarded a University of Toronto COVID-19 Student Engagement Award for their project titled Network and evolutionary analysis of SARS-CoV-2: A vaccine perspective. Together, they will develop new machine learning tools to analyze the SARS-CoV-2 genome and how it evolves.
“We’re two like-minded individuals with complementary skillsets who enjoy coding, math and solving problems, which – fortunately – can be done remotely,” says Ouellette, who is a PhD Candidate in Dr. Philip Awadalla’s lab at OICR. “We saw the opportunity to help with COVID-19 research and we’re happy to apply our skills to help advance research towards new solutions for this pressing problem.”
Ouellette specializes in evolution and population genetics and Shaw specializes in network analysis and algorithm development. Through this award, they will investigate how SARS-CoV-2 is evolving by looking into specific regions of the virus’ genetic code from samples around the world, using mathematical modelling, machine learning, and evolutionary simulations. They are specifically interested in how these changes in the genetic code may alter the virulence, or severity, of the virus.
“Just like cancer, different pressures or stresses can make viruses evolve,” says Shaw, who is a PhD Candidate in mathematics at the University of Toronto. “Understanding these changes can have an impact on how we build vaccines. Furthermore, better understanding of the virus’ evolution may shed light on viral reinfection, which is an important issue as we move into the later stages of the pandemic.”
Ouellette and Shaw plan to publicly release the code that they develop through this initiative for other researchers to build upon.
“SARS-CoV-2 has a much simpler genome than a cancer genome, so it can serve as a simplified model to test out new analytical techniques,” says Ouellette. “Ultimately, I hope to bring the tools and technology we create back into my research on cancer so we can better understand how cancer evolves and becomes resistant to treatment.”
August 31, 2020
Learn about the research that the Ontario Health Study has been doing during COVID-19 and how scientists have managed to do this work from home.
August 28, 2020
In the most comprehensive analysis of whole cancer genomes to date, OICR researchers identify novel sex-linked genomic differences that may be able to predict cancer severity and response to therapy
Cancer differs in males and females but the origins and mechanisms of these differences remain unresolved. A better understanding of sex-linked differences in cancer could lead to more accurate tests and allow sex to be included as a consideration when personalizing treatments for patients.
In a study, published in Nature Communications, OICR’s Constance Li and collaborators identify key genetic characteristics that differ between sexes. Here, Li describes what they found and what this means for patients.
Some studies have already hinted that cancer genomes differ between males and females. What is new about this study?
Previous studies focused on the exomes of patient tumours. That means that they were only looking at a small fraction of the genome that codes for proteins. This study allowed us to look at the entire genome – all of our DNA code – and take a dive deep into many aspects of the disease, like how tumours evolve over time.
By looking at the entire genome and in this ‘dark space’ that we hadn’t explored, we were able to confirm some previous findings but also find new differences between male and female tumour samples.
What sort of differences did you find?
We catalogued the differences we found across nearly 2,000 patient tumours representing more than two dozen different cancer types. Interestingly, we found that biliary cancers – like some liver, gall bladder and bile duct cancers – evolve differently in males than they do in females.
We also found that mutations in the TERT promoter – which is a hot topic in cancer research – occur much more often in men than in women, especially in thyroid cancers.
What does this mean for researchers who are looking into this subject?
Our findings suggest that there are underlying biological differences in the way that male and female tumours begin and progress. Overall, we need to be aware of these differences and consider the sex differences as we develop new tools that can match patients to appropriate treatments.
How else could this be helpful for cancer patients?
These findings are preliminary but powerful. It is important to note that more clinical data and research are needed to validate the differences we found. Ultimately, if we look deeper and find that a cancer progresses along one course in females and a different course in males, we can design roadblocks – or therapies – to stop the cancer along that specific course for that sex.
This paper is part of the Pan-Cancer Analysis of Whole Genomes Project. Read more about the Pan-Cancer project here.
August 28, 2020
OICR-supported researchers and collaborators discover indicators in the blood that may predict which patients will respond to the immunotherapy drug, pembrolizumab
Adapted from UHN’s Media Release.
Immunotherapy can shrink tumours and prolong survival for certain cancer patients, but clinicians don’t yet know which patients will benefit from these treatments. OICR-supported researchers and collaborators at the Princess Margaret Cancer Centre have made a discovery that could help identify those patients who may benefit and match them with potentially life-saving therapies.
In their study, recently published in Nature Cancer, the research group found that the changing levels of tumour fragments, or circulating tumour DNA (ctDNA), in a patient’s blood can be used to predict whether they will respond to the immunotherapy drug pembrolizumab.
The study lays the foundation for researchers to develop an easy, non-invasive and quick blood test to determine who will benefit from the drug and how well their disease is responding to treatment.
“While we have known for some time that cancer disease burden can be monitored by measuring tumour DNA in the blood, we are excited to report that the same concept can be applied to track the progress of patients being treated with pembrolizumab,” says co-first author Cindy Yang, PhD Candidate in Dr. Trevor Pugh’s lab at the Princess Margaret Cancer Centre and OICR. “This will hopefully provide a new tool to more accurately detect response and progression in patients undergoing immune checkpoint inhibitor therapy. By detecting progression early, patients may have the opportunity to undergo subsequent lines of treatment in a timely fashion.”
The benefits of blood tests
Conventionally, imaging scans – such as computerized tomography (CT) scans – and other methods are used to monitor a patient’s cancer. This study suggests a simple and quicker blood test as an alternative to these scans.
“Although important, computerized tomography (CT) and other scans alone will not tell us what we need to know quickly or accurately enough,” says senior author Dr. Lillian Siu, Senior Scientist and medical oncologist at the Princess Margaret Cancer Centre.
Dr. Scott Bratman, radiation oncologist and Senior Scientist at the Princess Margaret Cancer Centre and co-first author of the study, points out that it may take many months to detect whether a tumour is shrinking with various imaging scans.
“New next-generation sequencing technologies can detect and measure these tiny bits of cellular debris floating in the blood stream accurately and sensitively, allowing us to pinpoint quite quickly whether the cancer is active.”
This study represents one of the many emerging applications of using ctDNA to guide treatment decisions. It is one of the first to show that measuring ctDNA could be useful as a predictor of who responds well to immunotherapy across a broad spectrum of cancer types.
The prospective study analyzed the change in ctDNA from 74 patients, with different types of advanced cancers, being treated with pembrolizumab. Of the 74 patients, 33 had a decrease in ctDNA levels from their original baseline levels to week six to seven after treatment with the drug. These patients had better treatment responses and longer survival. Even more striking was that all 12 patients who had clearance of the ctDNA to undetectable levels during treatment were still alive at a median follow-up of 25 months.
Conversely, a rise in ctDNA levels was linked to a rapid disease progression in most patients, and poorer survival.
“Few studies have used a clinical biomarker across different types of cancers,” says Siu, who also co-leads OICR’s OCTANE trial. “The observation that ctDNA clearance during treatment and its link to long-term survival is novel and provocative, suggesting that this biological marker can have broad clinical impact.”
Innovation and translation
This study is part of a larger flagship clinical trial, INSPIRE, which has enrolled more than 100 patients with head and neck, breast, ovarian, melanoma and other advanced solid tumours. INSPIRE brings together researchers from many disciplines to investigate the specific genomic and immune biomarkers in patients that may predict how patients will respond to pembrolizumab.
INSPIRE is made possible by collaborations across institutes and industries with expertise from those applying genomics to research and those applying genomics in the clinic.
“INSPIRE is an incredibly collaborative initiative that is a blend of big genomics – looking at large trends across many individuals – and highly-personalized genomics – looking at mutations within each patient sample,” says Pugh, co-senior author, Senior Scientist at Princess Margaret and Senior Investigator and Director of Genomics at OICR. “This is a modern approach to the translation of clinical genomics.”
“As a PhD student, this project gave me the unique opportunity to work in a highly collaborative intersection with industry, clinical, and academic partners,” says Yang. “It is very exciting to see translational research in action.”
Read the UHN Media Release.
August 28, 2020
The tools behind the treatment: Building image-guided devices for more accurate and effective cancer procedures
OICR-supported researchers develop multi-purpose AI algorithm to help track needle placement and improve the accuracy of several image-guided treatment techniques
Cancer patients often encounter many needles, some of which are used to collect tissue samples or deliver therapy directly to a tumour. Specialists who carry out these procedures are trained to place needles precisely in the correct location, but what if we could give these specialists a real-time GPS for needles? Would biopsies be more accurate? Could needle-related therapies be more effective?
Dr. Aaron Fenster’s lab is working to develop tools for these specialists to guide their needles and ultimately improve the accuracy of biopsies and therapies for patients. In their recent paper, published in Medical Physics, they describe their new deep learning method to track needles in ultrasound images in real time.
“It may be surprising to many individuals, but a lot of these procedures are still done based on skill alone and without image processing,” says Dr. Derek Gillies, medical physicist in training and co-first author of the paper. “We’re working to provide clinicians with tools so they can better see their needles in real time rather than going in blind for some procedures.”
The deep learning methods presented in this paper are applicable to many types of needle procedures, from biopsies – where a clinician draws a tumour sample from the body – to brachytherapy – where a clinician delivers radiotherapy directly to the tumour. The methods could also be applied to several cancer types including kidney cancer, liver cancer and gynecologic cancers.
“Developing artificial intelligence algorithms requires a lot of data,” says Jessica Rodgers, co-first author of the paper and PhD Candidate at Western University’s Robarts Research Institute. “We didn’t have a lot of imaging data from gynecologic procedures, so we decided to team up to develop a method that could work across several applications and areas of the body.”
“That’s the most exciting aspect of this effort,” says Gillies. “To our knowledge, we were the first to develop a generalizable needle segmentation deep learning method.”
Now, members of the Fenster lab are working to integrate these algorithms into the video software equipment used in the clinic.
“Our work is giving clinicians new tools, which can help them make these procedures more precise and more accessible,” says Rodgers. “These tools could ultimately help lead to fewer missed cancer diagnoses and fewer patients with cancer recurrence.”
August 25, 2020
OICR-supported researchers demonstrate new drug may eliminate triple negative breast cancer cells in certain patients, discover a new method to identify which patients will benefit
Adapted from UHN’s Media Release.
Triple negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer that often spreads to other organs and accounts for one in four breast cancer deaths. OICR-supported researchers at the University Health Network’s Princess Margaret Cancer Centre are zeroing in on the molecular mechanisms that fuel this deadly cancer’s runaway growth to develop more effective treatments for this disease.
In their study, recently published in Nature Communications, they found a promising approach that could potentially identify the patients who could benefit from a more precise, targeted therapy for TNBC.
“This disease has no precision medicine, so patients are treated with chemotherapy because we don’t have a defined therapeutic target,” says co-lead of the study Dr. Mathieu Lupien, Senior Scientist at the Princess Margaret Cancer Centre and OICR Investigator. “Initially, it works for some patients, but close to a quarter of patients recur within five years from diagnosis, and many develop chemotherapy-resistant tumours.”
“These savage statistics mean that we must improve our understanding of the molecular basis for this cancer’s development to discover effective, precise targets for drugs, and a companion test to identify which patients are most likely to benefit the most from such a therapy.”
The study investigated how TNBC cells are dependent on a specific protein called GLUT1 and its associated molecular pathways. Prior studies suggested that TNBC cells were dependent on GLUT1, but this study is the first to demonstrate that blocking GLUT1 function may be an effective therapeutic strategy for certain patients with TNBC.
Using a collection of cell lines, the researchers found that blocking this pathway with a drug-like chemical compound “starved” the cancer cells, but only in a subset of TNBC patient samples. The group investigated further and found a common trait between the cell lines that were sensitive to the drug – they had high levels of a protein called RB1. This indicates that patients with TNBC and high levels of RB1 may, one day, benefit from this drug.
“Having access to diverse cell models of triple-negative breast cancer allows us to distinguish where the potential drug will work, and where it won’t,” says Lupien. “Without this broad spectrum of samples, we might have missed the subset of triple-negative breast cancers that respond to our compound.”
Collectively, this study suggests that clinical evaluation of targeting GLUT1 in certain patients with TNBC is warranted.
“The more we understand about the molecular complexity of cancer cells, the more we can target with precision,” says co-lead of the study Dr. Cheryl Arrowsmith, Chief Scientist for the Structural Genomics Consortium Toronto laboratories and Professor of Medical Biophysics at the University of Toronto. “And the more we can build up a pharmacy of cancer drugs matched to specific changes in the cancer cell, the greater the chance of a cure.”
Read UHN’s Media Release.
July 29, 2020
OICR welcomes Dr. Courtney Jones to Ontario’s cancer research community
Starting up an independent research lab in the midst of a pandemic is difficult but Dr. Courtney Jones is up for the challenge. Jones moved to Canada prior to the lockdown and has been gearing up for new experiments since. Now, as an OICR Investigator, she has safely started working in her lab at the Princess Margaret Cancer Centre to find new solutions for the leading cause of leukemia deaths in Canada – acute myeloid leukemia (AML).Continue reading – Q&A with new OICR investigator Dr. Courtney Jones on benefitting patients through research
July 27, 2020
Evolving treatment to evolving tumours: How OICR-supported researchers are getting ahead of ovarian cancer
OICR-supported Phase II trial uncovers how ovarian cancers become resistant to treatment, identifies new opportunities to personalize treatment for future patients
Clinician investigator Dr. Stephanie Lheureux has seen many women fight ovarian cancer – some who overcome the disease and unfortunately many who die. These women inspire Lheureux to find new effective treatments and to continue improving how we treat the disease.
One remarkable patient inspired the EVOLVE trial. After years of keeping her ovarian cancer in check, her cancer began to grow again, indicating that it had become resistant to the maintenance treatment she was on. Lheureux presented the option of palliative chemotherapy, as the latest guidelines suggest, but her patient declined – she wanted a different treatment that would allow her to have a healthy life outside of the hospital.
“This type of chemotherapy requires several visits to the hospital and it’s associated with side effects on patients’ hair, skin and nails,” says Lheureux, Clinician Investigator at the University Health Network’s Princess Margaret Cancer Centre. “This patient didn’t want to go on standard chemotherapy. She had participated in several clinical trials before, and she urged me to find her another option.”Continue reading – Evolving treatment to evolving tumours: How OICR-supported researchers are getting ahead of ovarian cancer
July 24, 2020
OICR research leads to new pancreatic cancer clinical trial with aim to change the standard of care for patients
New pancreatic cancer trial, NeoPancONE, launches across Canada
Adapted from Pancreatic Cancer Canada’s press release.
OICR’s PanCuRx team and collaborators have launched NeoPancONE, a Phase II clinical trial that will evaluate a potentially curative treatment strategy for operable pancreatic cancer. The trial, which is supported by Pancreatic Cancer Canada, will recruit patients at 10 cancer centres across the country to evaluate the effectiveness and feasibility of peri-operative chemotherapy – chemo treatment before and after surgery.
Typically, only 50 per cent of pancreatic cancer patients receive chemotherapy after surgery due to a range of personal and health reasons. NeoPancONE will help evaluate whether chemotherapy treatment before surgery can help extend the lives of these individuals.Continue reading – OICR research leads to new pancreatic cancer clinical trial with aim to change the standard of care for patients
July 23, 2020
Prevention before treatment: How an OICR investigator is shifting the paradigm of chronic disease in Canada
The BETTER Program for chronic disease prevention and screening now customized for young adults, women and cancer survivors across the country
Cancer doctors are extensively trained to find and treat the disease, but what about preventing cancer in the first place?
Dr. Eva Grunfeld is dedicated to making prevention a priority.
In 2012, Grunfeld established the BETTER Program and today, this Canada-wide initiative is expanding and adapting to serve more individuals across the country.
Since its inception, BETTER has trained nearly 250 health professionals to become Prevention Practitioners who specialize in chronic disease prevention and screening. These Prevention Practitioners work in the primary care setting to develop personalized “prevention prescriptions” that are tailored to each patient based on an in-depth analysis of their medical history, family history, lifestyle factors, and other risk factors for diabetes, cardiovascular disease and cancer.Continue reading – Prevention before treatment: How an OICR investigator is shifting the paradigm of chronic disease in Canada
July 21, 2020
OICR researchers and collaborators awarded $520,000 in new funding for COVID-19 drug discovery project
OICR Scientific Advisor and Group Leader, Dr. Gennady Poda, and collaborators at Sunnybrook Research Institute have been awarded $520,000 to identify new therapeutics and existing drugs that could be repurposed for the treatment of COVID-19. This award, which was announced on July 17 by Premier Doug Ford, is part of the Government of Ontario’s $20 million COVID-19 Rapid Research Fund.
Using OICR supercomputers and advanced computational chemistry techniques, Poda and collaborators aim to identify drugs that can stop the virus from replicating in the body by targeting the virus’ key polymerase enzyme, RdRP.
“We’ll be looking for new potential drugs to treat the COVID-19 infections by rapidly identifying approved drugs and compounds that are in clinical trials that could inhibit RdRP,” says Poda. “We will advance the most promising compounds into preclinical animal models and, if the data is promising, into patients.”Continue reading – OICR Drug Discovery awarded for COVID-19 research