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.
May 25, 2020
OICR-funded researchers pinpoint short-lived cells that give rise to childhood brain tumours
Childhood brain tumours are remarkably complex, but understanding their origins could help researchers develop drugs to eliminate them. Where can these cells be found? How early do they appear? How do they lead to tumours? For Dr. Hayden Selvadurai, these unresolved questions were a call to action.
In a recent study, published in Cell Reports, Selvadurai and collaborators at The Hospital for Sick Children (SickKids) discovered a rare type of stem cell that gives rise to medulloblastoma, the most common type of brain cancer in children. Their study shows that these cells arise early in brain development and exist for a brief period of time – a developmental window which scientists can now home in on.
“If we can’t eliminate the stem cells at the root of medulloblastoma, we can’t effectively treat the disease,” says Selvadurai, who was a Postdoctoral Fellow under the supervision of Dr. Peter Dirks while leading this study. Dirks is Head of the Division of Neurosurgery at SickKids, Principal Investigator at The Arthur and Sonia Labatt Brain Tumour Research Centre, Professor at the University of Toronto and Co-leader of OICR’s Brain Cancer Translational Research Initiative (TRI). “These problematic cells arise amid a complex and intricate process of fetal brain development and we were able to pinpoint exactly when that happens.”
The study builds on the research group’s previous publication in Cancer Cell that traced the origins of medulloblastoma growth back to a small group of cells that distinctively expressed the SOX2 gene. Using single-cell RNA sequencing, lineage tracing and advanced imaging techniques, the team showed that these stem cells were responsible for generating all other tumour cells and could give rise to new tumours if not fully eliminated.
“I’m proud of these findings because we were able to unify our knowledge of developmental neurobiology with cancer biology,” says Selvadurai. “We were able to build on our understanding of medulloblastoma growth while improving our experimental models of brain cancer. Together, this work could help the community develop new effective treatments for patients with the disease.”
Dirks’ research group plans to further investigate the genes involved in the early stages of medulloblastoma in collaboration with OICR’s Brain Cancer TRI team.
This study was supported in part by the Canadian Institutes of Health Research and OICR through the Stand Up to Cancer (SU2C) Canada Cancer Stem Cell Dream Team.
May 21, 2020
The Ontario Tumour Bank’s longstanding leader appointed Secretary of International Society for Biological and Environmental Repositories
The International Society for Biological and Environmental Repositories (ISBER) today announced the appointment of Monique Albert as Secretary of the Society’s Board of Directors.
With two decades of experience in research and biobanking and three years of experience on the Society’s Board as Director-at-Large Americas, Albert has been re-elected to the Board into the executive role of Secretary.
In her new position, Albert will lead the maintenance of ISBER by-laws, policies and procedures affecting nearly 1,000 ISBER members who lead hundreds of biobanks around the world. While assuming this role, Albert will continue to serve as Director of the Ontario Tumour Bank at OICR, a position that she has held for more than seven years.
Here, she reflects on her new role and her experiences to date.
How did you become involved in preserving human specimens for research?
MA: I began working directly with human specimens as a researcher in 2001, using cutting-edge technologies to analyze human samples. It was through this experience that I realized the utmost importance of preserving and maintaining the quality of these specimens to generate the most reproducible data. Good biological science is built on good data, which can only come from well-preserved samples.
When I recognized the importance of these invaluable samples, I began developing initiatives to improve biobanking practices at my local research institute. I’ve been building on those initiatives ever since.
Quality is an important aspect of your work. How do you make quality maintenance sustainable?
MA: While sample quality is a key element of a biobank’s success, it is not the only one that matters. To be successful, a biobank needs to meet current and future research needs, comply with standards and regulations, and operate in a sustainable way for future generations. I’m fortunate to have a background in project management and business planning that helps balance these three elements with limited resources.
As biobanking has become more mainstream, I’m proud that Ontario has consistently been at the forefront of biobanking standards. I’ve had the privilege of sharing my work with the growing international biobanking community through presenting at conferences and publishing on several occasions.
What are you looking forward to in your new role as Secretary?
MA: Having plenty of experience with ISBER – and ISBER’s savvy, inclusive and collaborative members – I know we are making an incredible impact on research. I’m honoured to be elected to this role and to continue to volunteer my time for the continued growth of ISBER. My previous experience at ISBER will allow me to hit the ground running and keep the momentum on existing goals and initiatives with the best interests of the Society and its members at heart.
May 20, 2020
Local research group discovers a new way to shut down a pair of cancer-driving proteins, pontin and reptin, using the structure of an FDA-approved drug
Pontin and reptin are proteins that are involved in several cancer-driving mechanisms and play key roles in several diseases, including liver, colorectal, breast, lung and bladder cancers. This makes them a hot target for cancer drug development and discovery efforts. Currently, there is only one drug class that may hold some promise to shut down these proteins, but a Toronto-based team of scientists has recently broken new ground.
Dr. Walid Houry’s Lab at the University of Toronto and OICR’s Drug Discovery group have discovered that pontin and reptin, also known as RUVBL1 and RUVBL2, may be blocked to prevent cancer growth using a chemical similar to the FDA-approved drug, sorafenib. Their findings, which were recently published in Biomolecules, could be a starting point for new and improved cancer drugs based on the approved drug’s structure and function.
“Through our research, we detangled a large, complex process of interactions between proteins, but what we found was both rewarding and exciting,” says first author Dr. Nardin Nano, who was a PhD student in the Houry Lab while leading the study. “Our findings suggest a new target for cancer treatment and that a new therapy could be within reach.”
This study is part of a larger initiative, led by Nano and members of the Houry Lab, to further describe the function of these proteins in helping cancers grow and invade tissues. With their newfound understanding, the Houry Lab will continue to design and develop molecules similar to sorafenib that can better target pontin and reptin.
“I look forward to future studies that will use this knowledge to better inhibit these proteins in vivo,” says Nano. “Although there is more work to be done, I’m proud that this discovery can help guide future drug development efforts.”
“Given the multiple roles of pontin and reptin in carcinogenesis, it’s not surprising that they are promising drug targets,” says Houry, who is a Professor at the University of Toronto and supported by OICR’s Cancer Therapeutics Innovation Pipeline. “These findings motivate us to continue developing pontin and reptin inhibitors as potential anti-cancer compounds that could – one day – help a number of patients with the disease.”
May 13, 2020
Toronto researchers unravel key cancer-driving circuit between the “powerhouse” and the “brain” of leukemia cells, in big first step for future therapeutic discovery and development
Over the last few decades, research has suggested that mitochondria, also known as the “powerhouses of the cell”, play an important role in tumour growth and development, but little is known about how to prevent these cellular machines from wreaking havoc. In a recent study, scientists have discovered a key protein that is made in the “powerhouse of the cell”, unexpectedly affects the expression of genes in the nucleus, or the “brain”, of certain leukemia cells. The study was launched by Dr. Dilshad Khan, who – alongside colleagues in Dr. Aaron Schimmer’s lab at the Princess Margaret Cancer Centre – set out to determine which genes in the mitochondria were essential to the growth and viability of acute myeloid leukemia (AML).
Through genome-wide CRISPR screening and other gene-manipulating techniques, they discovered a key mitochondrial protein that AML cells can’t survive without – MTCH2. Their findings, which were recently published in Blood, may eventually lead to new ways to fight this common and fast-growing form of blood cancer.
“We found that the mitochondrial protein MTCH2 is essential for the growth and survival of AML cells,” says Khan, Postdoctoral Fellow in the Schimmer Lab, who is the first author of the study. “But finding this protein was just one piece of the puzzle. We needed to understand how it worked.”
With Khan’s expertise in epigenetics, the team systematically dissected how MTCH2 affects AML cells. They found that blocking this protein would ultimately cause leukemic stem cells – the difficult-to-treat renewable cells that are thought to be at the root of leukemia – to irreversibly transform into cells that are easier to eliminate with existing chemotherapies.
“Through a series of experiments, we unraveled how MTCH2 affects AML cells and discovered that this protein has a remarkable and unexpected impact on nuclear pathways – it could control nuclear gene expression to affect AML stemness and survival,” says Khan. “We never thought this could happen, but now that we’ve discovered these new links, we could potentially find new ways to control these mechanisms.”
Next, the Schimmer Lab and collaborators plan to investigate MTCH2’s specific mechanism to find where inhibitors – or potential cancer drugs – could block its path. These initiatives will add to Schimmer’s research on dysregulated mitochondrial pathways in leukemia, including his recent work on fat production and copper distribution in leukemic stem cells. This research is funded in part by OICR’s Acute Leukemia Translational Research Initiative and OICR’s Cancer Therapeutics Innovation Pipeline.
“This study showed us that mitochondrial proteins are more interconnected with other cellular networks than we thought,” says Khan. “These fundamental findings have shed light on new research avenues that we can pursue to find new solutions that will hopefully benefit patients with AML.”
May 6, 2020
OICR-supported study helps move promising CAR-T cell therapy into a first-in-child clinical trial
Recurrent brain tumours are some of the most difficult cancers to treat, with no approved targeted therapies available and only a few potential therapies in clinical trials. Developing new drug treatments for these tumours is challenging in part because the drugs must overcome the blood-brain barrier and specifically target cancer cells while sparing the surrounding critical regions of the brain. Scientists at The Hospital for Sick Children (SickKids) have discovered a new solution.
In a study, recently published in Nature Medicine, a SickKids-led research team describes a novel treatment approach that delivers chimeric antigen receptor T (CAR-T) cell therapy directly into the cerebrospinal fluid that surrounds the tumour. Their findings show that the approach was effective in treating ependymoma and medulloblastoma, two common types of brain tumours, in experimental mouse models of human disease.
“The vast majority of children with recurrent metastatic medulloblastoma or ependymoma currently have a deadly prognosis, so it is very exciting to think we have identified a novel approach to treat this underserved patient population,” says senior author Dr. Michael Taylor, Neurosurgeon, Senior Scientist in the Developmental and Stem Cell Biology program and Garron Family Chair in Cancer Research at SickKids and Co-lead of OICR’s Brain Cancer Translational Research Initiative.
CAR-T cell therapies, which use genetically engineered immune cells to attack cancer cells, are remarkably effective in treating certain types of lymphomas and leukemias. Whereas CAR-T therapies are typically delivered through the blood stream, the research team discovered that delivering their engineered T cells directly into the cerebrospinal fluid provided a better chance for the therapy to reach and eliminate brain tumours.
The team performed in-depth molecular studies to design CAR-T cells that can recognize specific molecules on the surface of brain tumour cells. They also found that the use of a complementary approved cancer medication, azactyidine, boosts the efficacy of their approach.
Now, building on these findings, collaborators at Texas Children’s Hospital have launched a first-in-child clinical trial to test the safety and anti-tumour efficacy of their new strategy.
“This work was possible thanks to the concerted collaboration of our Pediatric Cancer Dream Team, which brought together scientists studying tumor genomics and tumor immunotherapy around the world to enable the design of more effective therapies for children with incurable and hard to treat cancers,” says corresponding author Dr. Nabil Ahmed, associate professor of pediatrics and immunology, section of hematology-oncology at Baylor and Texas Children’s Hospital.
This research was supported in part by OICR through OICR’s Brain Cancer Translational Research Intitiative and funding provided to the Stand Up to Cancer (SU2C) Canada Cancer Stem Cell Dream Team.
May 6, 2020
I hope that everyone has continued to stay safe and healthy as the world continues to grapple with the risks and challenges presented by COVID-19. The impacts of the pandemic have been felt by individuals and organizations across society, including cancer patients and Ontario’s cancer research community.
While things are obviously not business as usual, I am happy to see OICR’s people rise to the challenge and find solutions to allow us to continue to focus on cancer research while working remotely. My thanks go to OICR’s staff, Board and Scientific Advisory Boards, collaborators and others who have quickly adapted to continue our work as best we can. A big thank you also to our funders at the Ministry of Colleges and Universities for their continued support. We will gradually restore our onsite cancer research activities in a manner that will ensure a safe work environment for all our onsite staff. Our priority remains to improve the lives of those with cancer through research.
OICR’s leadership recognizes that the pandemic has resulted in unprecedented challenges for cancer researchers across Ontario. We have taken steps to ease this burden and are working with OICR-funded researchers and partner organizations to overcome these challenges together. More information about how we are assisting our funded researchers can be found on our website.
Due to our collaborative, cross-disciplinary research strengths, OICR is well-situated to contribute to COVID-19 research. OICR researchers are engaged in numerous projects with others in Ontario and abroad. It has been heartening to see such a swell of collaborative spirit and to see the research community doing what we can to help overcome COVID-19. I invite you to visit our website to learn more about how OICR is doing its part. We are especially cognizant on how these research activities impact cancer patients, as they are an especially vulnerable population at this time.
COVID-19 has disrupted cancer research on a global scale. I look forward to a time when we can resume all of our research activities and once again contribute to the international campaign against cancer at full capacity. During the pandemic, cancer has not and will not cease to be a reality for the thousands of Ontarians living with this disease and their families. Everyone at OICR remains steadfast in our commitment to improve the lives of those facing cancer.
In closing, I offer my deepest appreciation to all those working on the front lines of this crisis and thank all off the members of Ontario’s cancer research community for their continued dedication during this difficult time. All our thoughts also go out to any families that have been affected during this crisis.
Dr. Laszlo Radvanyi
President and Scientific Director
April 29, 2020
The province’s oncology-specialized research ethics board honours Janet Manzo’s contributions as she retires and welcomes new Executive Director, Natascha Kozlowski
Since 2006, two years after its inception, Janet Manzo has led the Ontario Cancer Research Ethics Board (OCREB) as Executive Director. Through her tireless commitment to research ethics, she has established OCREB as a leading central research ethics board for the province that is also widely recognized across the country for its innovative model and approach to research ethics. Manzo has recently announced her retirement and joins OCREBs members its Advisory Committee in welcoming Natascha Kozlowski to succeed her as Executive Director.
Kozlowski, who is the former Director of Research at Lakeridge Health, a five-site hospital system serving Durham Region, brings nearly two decades of experience in clinical research to OCREB’s leadership team.
We sat down with Manzo and Kozlowski to discuss changes in research ethics since OCREB was established and OCREB’s next chapter.
How have cancer clinical trials and ethics processes evolved in Ontario since OCREB began?
Janet Manzo (JM): OCREB was essentially like a start-up. When it was created, there was no model like it in Canada. OCREB has radically changed the research ethics environment for multi-centre cancer trials in Ontario. Today, OCREB enables research by streamlining the review process, minimizing redundancy in hospitals across Ontario, promoting consistency, and saving time and costs by serving as a specialized, consolidated committee for ethics reviews.
Looking back over these years, it’s clear that cancer clinical trials have become more complex. For example, we’ve seen new and innovative study designs, more and more thorough consent forms, more frequent inclusion of quality-of-life assessments, and increases in biologic specimen collection for biomarker development, genetic testing and future research. I’m grateful to have had the opportunity to lead OCREB operations for more than fourteen years, a period of constant growth and change, leading to a successful and well-respected model of ethics review for multi-centre cancer research.
Natascha Kozlowski (NK): From my experience as the Director of Research at a large hospital, I witnessed – on the ground level – how OCREB positively impacts cancer research at hospitals. I can attest that OCREB has helped improve research ethics processes at sites across Ontario while enabling life-saving, ethically-sound clinical research.
How does OCREB adapt to changes in cancer clinical trials?
JM: For research ethics boards, the increasing complexity of clinical trials means it is more important than ever to stay current and to have the right expertise around the table, such as experts in pathology or genetics. OCREB has and will continue to evolve as new cancer technologies and clinical trial designs emerge.
NK: To echo Janet: new clinical trial designs bring new ethical considerations to the table. I think Janet has set up a tremendous organization with a great network of support – OICR included – that can continue evolving to enable innovative research.
JM: I’d like to thank all of the OCREB staff, advisors and members for their unfailing support and for their steadfast dedication to the protection of research participants. I will miss everyone but I am confident that OCREB is in good hands.
What does the future hold for OCREB? What are you looking forward to the most?
NK: OCREB has a strong history of excellence in the clinical trial environment, often being consulted as a respected source of ethics guidance. I look forward to working with our Members and Advisory Committee in the years to come to uphold and strengthen OCREB’s reputation while advancing cancer research.
I would like to express my sincerest thanks to Janet Manzo for many years of dedication and leadership in building an outstanding research ethics board. Over the years, Janet has earned the trust and respect of OCREB’s many members – including clinicians, researchers, ethicists, privacy experts, and community members – while serving Ontario’s cancer research hospitals and centres. I wish Janet all the best as she begins her retirement.
April 16, 2020
Former OICR intern leads the development of a COVID-tracking site used by more than 400,000 people in Canada to date
Flatten is quickly becoming a go-to source of information about how COVID-19 is spreading across Canada.
In less than a month, more than 400,000 people have submitted data on their symptoms, travel history, age and medical conditions, making Flatten the country’s leading crowdsourced COVID data repository.
Behind the project is a team of first- and second-year university students who are determined to help.
“We just wanted to put our technical skills to good use during this time,” says Vice President of Flatten, Yifei Zhang, in a University of Waterloo story. “It’s been great working together with everybody trying to build a platform that will be useful for Canadians across the country.”
As a web-based, data-gathering platform, Flatten provides a real-time heat map of self-reported confirmed and potential COVID-19 cases across the country. The platform helps increase awareness and flatten the curve of COVID-19 cases.
Over the last four weeks, Flatten has rapidly evolved from an idea into an incorporated non-profit organization, with support from advisors such as Dr. Geoffrey Hinton and sponsors such as Google Cloud, the Vector Institute and CIFAR.
The team behind Flatten has established collaborations with health authorities across Canada, such as in Montreal, and plans to work with other municipal governments and provinces..
“We work with leading advisors and collaborators to make sure we’re surveying the right questions and providing the right information for Canadians today to help flatten the curve,” says Zhang.
Zhang, who is completing his second year as a software engineering student at the University of Waterloo and leads Flatten’s website development, attributes his website development knowledge to his internship with OICR’s WebDev team.
“My time at OICR reinforced my interest in working in health and biology, giving me the motivation and drive to pursue this initiative,” says Zhang. “At OICR, I gained experience working with a high volume of data using robust techniques and I was able to bring that knowledge into developing Flatten.ca. A lot of the fundamentals we used to build this site came from best practices that I learned from my term at OICR.”
Learn more at flatten.ca.
April 8, 2020
Drs. Lisa Porter and John Trant from the University of Windsor are working to develop a drug to block a protein that is elevated in some types of aggressive cancer. Disrupting the activity of this unique protein complex could slow or stop the disease. By providing researchers such as Porter and Trant with funding support and access to expertise, OICR’s Cancer Therapeutics Innovation Pipeline initiative is enabling the development of the next wave of made-in-Ontario cancer therapies.
April 1, 2020
OICR-supported researchers quantify common prostate cancer outcome predictor
Advances in cancer research have opened the door to new tests to better assess tumours and help recommend the most appropriate course of treatment for a patient. Research pathologists play a critical role in turning scientific knowledge into tests that can be used in an everyday clinical setting.
“Scientists are constantly advancing our understanding of cancer, but that understanding cannot help patients unless it’s applied in practice,” says Dr. Tamara Jamaspishvili, Research Pathologist at Queen’s Cancer Research Institute. “Our role as research pathologists is to bridge that gap, and transform discoveries into more accurate diagnoses and prognoses for patients that could be implemented and actionable in practice.” Jamaspishvili’s work is supported by the Ontario Molecular Pathology Research Network, an OICR-funded province-wide network that conducts high-quality cancer research focussed on clinical impact.
An example of the challenge of clinical translation is found in PTEN testing. PTEN is a cancer-preventing gene that – when absent in a cell – may lead to uncontrolled tumour growth. Research has shown that the loss of PTEN within a prostate tumour could help predict the severity of a man’s prostate cancer, but PTEN is not routinely tested.
“Simply put, some cells in a tumour sample may have PTEN loss and some cells don’t, but nobody has clearly quantified how the ratio of cells with or without PTEN contribute to a patient’s health,” says Jamaspishvili.
Jamaspishvili teamed up with collaborators to address the subjectivity of PTEN testing. Her collaborators include Drs. David Berman, Palak Patel, Robert Siemens, Paul Peng, and Yi Niu from Queen’s Cancer Research Institute, Drs. Fred Saad and Anne-Marie Mes-Masson from the University of Montreal, Dr. Tamara Lotan from Johns Hopkins University, and Dr. Jeremy Squire and colleagues at the University of São Paulo.
Their study, recently published in the Journal of the National Cancer Institute, proposes a new quantitative approach to assess PTEN. They clarify how pathologists can predict the severity of a patient’s prostate cancer based on the number of cells with PTEN loss. These findings can help standardize PTEN testing, but their approach can also be applied to other pathology tests that are still highly subjective.
“Quantifying qualitative tests helps us move towards automated pathology techniques,” says Jamaspishvili. “This is the future of pathology.”
Jamaspishvili is now working to automate PTEN digital pathology analysis in collaboration with Dr. Stephanie Harmon and colleagues in Dr. Baris Turkbey’s lab as part of the National Cancer Institute’s Molecular Imaging Program.
“Now, we can apply machine learning image analysis tools to analyze PTEN loss and make better predictions for the benefit of patients. We look forward to using artificial intelligence in digital pathology to help fill the gaps between research and clinical practice.”
March 24, 2020
Ovarian and pancreatic cancer researchers join forces to debunk which treatments work for which patients
Ovarian and pancreatic cancer are some of the most challenging cancers to treat but their common characteristics have pointed to new treatments for certain subsets of patients. Drs. Stephanie Lheureux and Grainne O’Kane have teamed up to find out which patients can benefit from these new therapies.
Over the next year, with the support of an OICR Translational Research Initiative (TRI) Collaboration Award, Lheureux and O’Kane will be taking a deeper look into patient tumour samples that have a specific DNA damage repair deficiency, called homologous recombination deficiency (HRD). These tumours are thought to be sensitive – meaning, they can be eliminated – with a certain class of drugs called PARP inhibitors, but it is difficult to predict in the clinic whether a patients tumour has HRD or not. Further, it is difficult to determine whether a patient will benefit from using PARP inhibitors.
Lheureux, who is a medical oncologist specializing in ovarian cancers, and O’Kane, who is a medical oncologist specializing in pancreatic cancers, have set out to perform whole-genome analyses on patients with HRD to find a better way to identify which patients may respond to PARP inhibitors. Both researchers are excited to tap into each other’s expertise.
“Dr. Lheureux cares for many patients facing these challenges,” says O’Kane. “She has deep clinical expertise in this area.”
“Dr. O’Kane and her closest collaborators have excellent expertise in whole genome sequencing and bioinformatics,” says Lheureux. “We’re eager to work together.”
Their analyses may help them understand the biological mechanisms driving HRD and how HRD tumours become resistant to treatment. Their findings may also extend beyond ovarian and pancreatic cancers.
“We want to define the biological response to PARP inhibitors and the mechanism of resistance so that we can help these patients make the best treatment decisions for their specific disease,” says O’Kane.
“We’re motivated to redefine HRD and understand it on a deeper level to help us overcome resistance to treatment and extend the lives of those with these cancers,” says Lheureux.
Lheureux and O’Kane’s collaboration is supported by OICR’s TRI Collaboration Award, a pilot funding stream to support the training of young investigators and encourage collaboration amongst OICR’s TRI teams.