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.
June 2, 2020
Q&A with new OICR investigator Dr. Hartland Jackson on the latest in mass cytometry, single-cell imaging and his return to Canada
OICR welcomes Dr. Hartland Jackson back to Toronto as Lunenfeld-Tanenbaum Research Institute and OICR’s newest investigator
While he was a doctoral student developing experimental models of breast cancer, Dr. Hartland Jackson recognized the enormous potential impact of multiplexed imaging and single-cell technologies. If we could see how different cells interact within a tumour, what could we discover?
This question fueled his research over the last half decade, taking him to Switzerland to develop advanced imaging methods alongside experts at the University of Zurich. Now, returning to Canada, Dr. Jackson plans to collaborate across disciplines and sectors to apply this technology to solve more scientific and clinical questions. Here, he discusses his goal of bringing the benefits of this technology to more patients in Ontario and around the world.
What was your main research focus in Switzerland?
HJ: In a nutshell, I was developing a new technology, called imaging mass cytometry, which allows us to visualize and analyze tumour samples in more detail than ever before.
When I joined the research group at the University of Zurich, they had developed a prototype imaging system. My role was to take this system and be the first to apply it to a clinical problem. Ultimately, I helped shepherd the system from a prototype to a commercial product that is now used around the world.
What clinical application did you focus on?
HJ: I focused on investigating how this technology could help in the diagnosis and prognosis of breast cancer. Through this process, we made a lot of progress in developing analysis methods and optimizing the system. Whereas traditional imaging methods could see three or four markers on a cell, our system allows us to see 40 markers at the same time. With this technology and imaging system, we could visualize how different cells were organized within a sample, which revealed new types of breast cancer.
In addition to this discovery, my work showed that imaging mass cytometry can reveal information within clinical samples – meaning information that may be useful for patients. We pushed the boundary on what can be done with this system and now it’s used around the world to study different human diseases.
Interestingly, the technology that I was working on was an adaptation of an earlier technology developed in Toronto by DVS Sciences, which was supported in part by OICR. My plan was to work with the imaging experts in Switzerland and bring these developments back to the place where the technology was created and is now manufactured as a commercial product by Fluidigm.
Is that what brought you back to Canada?
HJ: Yes, one of the reasons I’ve returned to Canada is to bring this expertise back to Toronto. In addition to that, the research community here is very impressive. The universities, research institutes and hospitals are all tightly knit. This makes for an excellent environment to develop new technologies that can address clinical health challenges. I find that researchers here are like-minded in their goals and collaborative spirit. We enjoy working through technical challenges and delving into the mysteries of cell biology, and – at the same time – working on research that really matters to patients.
What will your future research focus on?
HJ: I plan to continue developing some of the methods that I was working on in Europe while expanding my research in a few exciting areas.
We’re looking to apply this technology to different types of cancer and different diseases in collaboration with clinician scientists. I’m interested in applying this technology in drug clinical trials to help us understand how patients respond to different therapies. In parallel, I look forward to using this technology to study experimental model systems to better understand how cells are communicating with each other and what goes wrong in the communication between cells during cancer development.
Our work has shown what this technology is able to do and that has only opened more avenues for future research. I’m excited because these new applications are now within our reach. To date, collaborations have allowed me to make more progress than I could have ever made on my own and I look forward to building new collaborations to make new discoveries in the future.
September 20, 2019
Ottawa cancer researchers and clinicians embrace the window of opportunity between a cancer diagnosis and treatment with a coordinated approach to clinical research
The time between a patient’s cancer diagnosis and their surgery presents a valuable “window of opportunity” to evaluate new treatment strategies. Short-term clinical trials during this period – also known as window of opportunity trials, window trials or phase 0 trials – can help researchers gain insights into the effects and the efficacy of a new potential treatment. Dr. Angel Arnaout at The Ottawa Hospital is putting window trials into practice.
“There are many nervous and anxious moments between diagnosis and their surgery but patients have limited options during this time,” says Arnaout.
“We saw an opportunity in this window of time to take action. We saw that we could help support patients who are waiting for surgery, while helping future patients through accelerating clinical research.”Dr. Angel Arnaout
Arnaout, a surgical oncologist who specializes in breast cancers, assembled a cross-disciplinary team of medical oncologists, pathologists and other clinical research specialists at The Ottawa Hospital to strategically design and implement this new approach. They would collectively establish common priorities, decide on which interventions would be tested and work to streamline the patient’s journey throughout the process.
Together, the team was motivated by the mutual benefits of all stakeholders involved. Namely, window trials can provide patients an opportunity to contribute and engage with cancer research while potentially improving the state of a patient’s disease. Meanwhile, these trials could ultimately expedite drug development by improving the understanding of a potential drug early in its development.
The team launched their first study in 2014, which found that patients were exceptionally eager to participate, and since then, launched and completed three additional window trials.
The first was a breast cancer trial on presurgical hormone therapy that helped establish the capacity and infrastructure for enrolling patients, organizing the investigations and giving patients short-term therapies. The second tested a potential cancer-fighting agent, chloroquine, and found that it had no effect on stopping breast cancer proliferation. The third trial debunked the idea that vitamin D – even at very high doses – can slow down the growth of breast cancer.
“These studies didn’t uncover a new therapy, but they did help us answer important questions that patients have, like ‘Will taking vitamin D help?’” says Arnaout. “These types of studies also provide a relatively quick method to test whether we should continue research into a particular avenue.”
The group at The Ottawa Hospital has recently teamed up with researchers from OICR to initiate a new breast cancer window-of-opportunity study to examine biomarkers of efficacy and resistance for another new drug candidate. The trial is planned to begin recruitment by mid-fall this year.*
Despite the benefits of these trials, Arnaout adds, it is still important to reduce unnecessary delays between diagnosis and surgery. Arnaout continues to minimize these delays at The Ottawa Hospital.
“We try our best to reduce wait times, but if patients have to wait – we can try to help them in the meantime while accelerating breast cancer research.”
*This new trial is co-led by Dr. John Hilton from The Ottawa Hospital and Dr. John Bartlett from OICR. Co-investigators include Drs. Laszlo Radvanyi, Melanie Spears, Arif Ali Awan, Mark Clemons, Greg Pond and Angel Arnaout.
July 30, 2019
Genome Canada, Ontario Institute for Cancer Research and Thermo Fisher Scientific to focus on pancreatic, prostate and breast cancer
CARLSBAD, Calif. – (July 30, 2019) – Genome Canada, the Ontario Institute for Cancer Research (OICR) and Thermo Fisher Scientific are collaborating to develop a complete solution of targeted next generation sequencing (NGS) assays and analysis software designed to more effectively assess – and eventually improve management of – pancreatic, prostate and breast cancer.
The $6 million, three-year initiative aims to standardize advanced molecular profiling in these disease areas and make the assays commercially available globally. Focusing on rapid genomic diagnostics in pancreatic cancer and targeting treatment in breast and prostate cancers, the partnership builds on previous clinical research between OICR and Thermo Fisher and will inform development of three assays that will be utilized to stratify patients in clinical trials in Ontario and other jurisdictions.
“By supporting research and clinical trials, Genome Canada is helping to put more of Ontario’s innovative cancer diagnostics research into clinical use,” said Dr. John Bartlett, program director, diagnostic development at OICR. “This project has the potential to springboard advanced next-generation sequencing to routine clinical use in Ontario and across Canada.”
Breast and prostate cancer are among the most common types of cancer in Canada, and the country’s five-year net survival rate for pancreatic cancer is only 8 percent. However, there is clear evidence that patient outcomes can be improved with NGS-based testing strategies. A recent U.S. health economics study has shown that advanced cancer patients who received treatment based on NGS testing results experienced double the length of progression-free survival without increasing health care costs.1
While some solutions analyze only DNA sequences, the new targeted NGS assays will provide comprehensive genomic profiles by simultaneously assessing DNA and expression signatures from RNA to provide significantly more insight into driver mutations. The OICR/Thermo Fisher team will leverage this advantage by supplementing the new assays with unique DNA/RNA stratification biomarkers – specific to pancreatic, prostate and breast cancer – previously qualified by OICR translational researchers.
The collaboration is partly funded with a grant from Genome Canada through the Genomic Applications Partnership Program (GAPP). Genome Canada will contribute $2 million, the highest possible level of funding support, with the balance split between OICR and Thermo Fisher, which will cover development costs and validation activities.
Previous research collaborations led by OICR and Thermo Fisher are already well on their way to impacting cancer treatment in the future. Of particular note is a 2016 study designed to identify mutations and copy number variation changes in breast cancer, and clinical research utilizing the Oncomine Comprehensive Assay, which also supports both the National Cancer Institute’s Adult and Pediatric MATCH trials in the United States.
“OICR is a leader in clinical research, with extensive clinical trials in progress to improve care for patients with pancreatic, prostate and breast cancer,” said Jeff Smith, global lead of NGS precision medicine initiatives, clinical NGS and oncology for Thermo Fisher Scientific. “When OICR approached our team with the idea for this project, we saw it as another exciting for opportunity to bring Thermo Fisher’s proven Ion Torrent technology to clinical laboratories across Canada and to contribute to future improvement of patient care.”
1 “A Retrospective Analysis of Precision Medicine Outcomes in Patients With Advanced Cancer Reveals Improved Progression- Free Survival Without Increased Health Care Costs,” Journal of Oncology Practice, Vol 13, Issue 2, February 2017
July 29, 2019
OICR researcher looks into what non-tumour cells can tell us about breast cancer
When a biopsy is drawn from a patient, it consists of a mix of cancerous and healthy cells, like fat and blood cells. Researchers are often interested in diseased cells, but without looking into the surrounding tissue, they could be missing part of the story.
Natalie Fox, a PhD candidate at OICR, is investigating what we can learn from the cells surrounding cancer cells.
“When we look into a patient sample computationally, we see distorted signals because of overlapping data from many different types of cells,” says Fox. “We need to dissect the parts we want to study, but instead of using a knife or a laser, we use computers.”
Fox and collaborators have analyzed nearly 1800 tumour samples from patients with breast cancer, examining the transcriptome of tumour cells and the cells around tumours – or the tumour’s microenvironment.
Her study, recently published in Nature Communications, reveals the landscape of transcriptomic interactions between breast cancers and their microenvironments. Her study also sheds light on associations between these transcriptomes and patient survival, gene mutations and breast cancer subtypes.
“We now have a clearer picture that tells us more about the breast microenvironment than we’ve known before,” Fox says. “Bit by bit, we’ve analyzed and scrutinized these data, then assembled these bits into a comprehensive landscape.”
Fox found that mutations in cancer genes such as CDH1 and TP53 are associated with changes in the transcriptome of the tumour’s microenvironment. She says more research is needed to clarify the biologic rationale behind her observations, but her work has set the stage for researchers to do so.
“Above all else, this work demonstrates an important approach for improving our understanding of associations between the tumour and the microenvironment,” Fox says. “We presented a framework that others can use to analyze the tumour microenvironment in their cancer of interest and potentially develop new biomarkers for predicting cancer patient outcomes.”
March 27, 2019
The winner of last year’s FACIT Falcons’ Fortunes pitch competition is already seeing early success in moving her product to the clinic
The winner will soon meet with U.S. regulators, marking a major step towards commercializing her innovative polymer product, ReFilx™, and bringing it to breast cancer patients.
It took only 10 minutes for a panel of investors and industry experts to recognize that Dr. Soror Sharifpoor and her oncology product – ReFilx™ – were worth supporting. Last spring, she pitched ReFilx™ in the FACIT Falcons’ Fortunes competition and won the top prize – the $50,000 Ernsting Entrepreneurship Award. Almost 12 months later, Sharifpoor and her team at Polumiros Inc. will be meeting with the U.S. Food and Drug Administration (FDA) to officially begin the regulatory submission process – a necessary first step in bringing their product to patients.
ReFilx™ is a polymer designed to fill the breast tissue cavities left in breast cancer patients following a lumpectomy. The polymer dissolves over time, allowing the patient’s cells and tissue to regrow in its space, thus preventing breast tissue defects from forming.
“ReFilx™ could improve the emotional and mental well-being of breast cancer patients,” says Sharifpoor. “In addition to the psychosocial benefits, it could also encourage surgeons to take more aggressive margins around the tumour, thereby reducing the chances of cancer recurrence.”
Bringing ReFilx™ to the clinic requires rigorous clinical testing and regulatory review, which begins with a pre-submission meeting with the FDA. FACIT’s support allowed Sharifpoor to continue with pre-clinical testing, hire a regulatory consultant and further develop ReFilx™ into an injectable form.
In a few months, Sharifpoor and her team will have the pre-submission meeting to collect feedback on their product, which will then be used to guide their future submission to the FDA and their plans for further clinical research. Polumiros Inc. intends to pursue this research in Canada.
“We’re excited to initiate our regulatory submission process,” says Sharifpoor. “We’re fortunate to have had FACIT’s support, allowing us to develop ReFilx™ faster and smarter than we would have on our own.”
FACIT, OICR’s strategic partner in commercialization, is hosting its 6th annual pitch competition this year on April 4, 2019. The Falcons’ Fortunes event will feature six aspiring entrepreneurs from across the province who are developing oncology-related innovations. FACIT runs the annual competition as part of its broader mandate to support translation of cancer research to benefit Ontario’s economy and patients worldwide.
Learn more about Falcons’ Fortunes – FACIT’s annual pitch competition or read about this year’s event details.
March 15, 2019
Expert researchers find shorter treatment cycles may reduce risk of breast cancer returning
Researchers have found that the dosage and interval of chemotherapy treatments have a significant impact on some breast cancer patients’ survival. For a very small minority of patients the difference of a week between chemotherapy treatments could mean the difference between life and death – and researchers are working to identify exactly who those patients are.
Over the last few decades, breast cancer clinical trials have investigated the way in which patients receive and respond to different chemotherapy dosing regimens. Some have tested if a shorter – but more intense – two-week treatment cycle is more effective than the standard three-week cycle. These trials, however, are often limited in size and do not have the statistical power to detect a difference in response to treatment.
Researchers from the Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) have recently performed a meta-analysis across 26 breast cancer trials to help clarify this dosing dilemma. As reported in The Lancet, they found that more intense dosing regimens were associated with a decreased risk of death from breast cancer and a decreased risk that the disease will return in some patients.
“As chemotherapy kills tumour cells, the residual – or remaining – cancer cells have more room to grow and tend to grow faster,” says Dr. John Bartlett, Program Director of Diagnostic Development at OICR and member of the EBCTCG Steering Committee. “These trials hypothesized that a more intense dosing regimen would give tumour cells essentially less room to grow. With the results of the EBCTCG overview study, we can say with confidence that a two-week treatment schedule will help to prevent death in a small portion of patients.”
The analysis found that approximately one in 50 women benefited from more intense dosing.
“The challenge now is to determine exactly which patients can benefit from intense dosing and which patients would not,” says Bartlett.
“If we can do so, we can prevent deaths due to breast cancer for some, while minimizing the negative side effects of intense chemotherapy for others.”
The ECBTCG is continuing to investigate dosing intensity in common breast cancer subtypes in parallel with researchers who are looking to find the biological basis of these differing responses to treatment.
“We’re in an era of de-escalation where we’re heavily invested in reducing overtreatment,” Bartlett says. “But this work helps us move towards an era of biologically rational treatment recommendations, one where breast cancer patients get the treatment they need at the right time and in the right way.”
November 22, 2018
Dr. Lorraine Lipscombe investigates why the 20 per cent of cancer patients with diabetes often experience worse outcomes
Several studies show that health outcomes – such as overall survival and preventable hospitalizations – are worse for cancer patients who also have diabetes. However, the reasoning behind this disparity is unclear. Dr. Lorraine Lipscombe, an endocrinologist at Women’s College Hospital and Diabetes Canada Investigator Award holder, is investigating why these differences exist and what we can do to avoid preventable complications.
October 24, 2018
Research team finds aggressive breast cancers are less frequent than previously thought, and less aggressive breast cancers need more of our attention.
Different subtypes of breast cancer respond to treatment differently and require different treatment approaches. Understanding the distribution of these subtypes and their respective clinical outcomes allows researchers to better understand the disease and identify key research priorities that may have been previously overlooked.
September 25, 2018
Breast cancer radiotherapy in a single visit provides more convenient option to patients, reduces burden of therapy
Cross-Canada research team moves image-guided ultrasound system into clinical development
Traditional breast cancer radiation treatment requires multiple hospital visits over a period of weeks or months, which may be onerous to patients who live far from hospitals or in remote communities. An alternative radiotherapy technique, Permanent Breast Seed Implantation (PBSI), requires only a single hospital visit, but it involves the implantation of multiple small radioactive metal pellets into the breast of the patient within millimetres of a target. The procedure to administer this treatment is difficult to plan and complex to execute – impeding the adoption of PBSI in the clinic.
September 24, 2018
OICR takes part in international multicentre study to standardize promising breast cancer digital pathology test
The Ki67 immunohistochemistry assay is a test that can help evaluate the aggressiveness of breast tumours, predict disease outcomes, monitor cancer progression and identify patients who are more likely to respond to a given therapy. Despite its potential to help patients with breast cancer, the analysis of Ki67 has not been widely adopted in the clinic, mostly due to the lack of standardization across laboratories.
July 10, 2018
Researchers further clarify the role of epigenetic proteins in the development of breast cancer, and discover that inhibiting these proteins could prevent the disease in women at high risk.