Dr. Laszlo Radvanyi, OICR’s President and Scientific Director, answers a question about precision medicine and discusses how OICR is working to improve access to this form of cancer treatment through the development of liquid biopsies.
New patient-centred system for brain cancer radiotherapy receives top honours at FACIT Falcons’ Fortunes
Dr. Hatim Fakir of London Health Sciences Centre won the 2024 pitch competition for his RadioSphere technology.
As a Medical Physicist, Dr. Hatim Fakir has seen first-hand how difficult radiosurgery can be for patients with brain tumours.
Radiosurgery is a specialized form of radiation therapy that uses precise, highly focused radiation beams to destroy tumours. It’s called “radiosurgery” because it achieves clinical results similar to surgery but without the need for incisions. But the intense radiation used to kill cancer cells can also harm nearby healthy tissue, which is especially risky in the brain and can result in severe side effects such as radiation necrosis and neurological deficits.
Though there are multiple technologies that aim to make radiosurgery safer and more precise, they aren’t effective at treating patients with complex diseases, such as having multiple tumours scattered in different parts of the brain. And today’s procedures often involve long, uncomfortable treatment session.
“Patients are often not feeling well, and they have to lay immobilized in rigid positions for a very long time,” says Fakir, who is based at Verspeeten Family Cancer Centre at London Health Sciences Centre. “I wanted to find a way to make treatments more effective, faster and more comfortable for patients.”
Fakir came up with a potential solution – a new ‘radiosurgery’ technology called the RadioSphere. With a unique, adaptable design, Fakir says the RadioSphere can target tumours of all different sizes, shapes and locations in less time than existing technologies.
He pitched his concept at FACIT’s 2024 Falcons’ Fortunes pitch competition, alongside five other teams of Ontario innovators, and was selected by the panel of judges as this year’s winner.
He will receive the $100,000 Ernsting Entrepreneurship Award, as well as ongoing guidance from FACIT, to help commercialize his made-in-Ontario innovation and bring it to the patients who need it. FACIT’s Prospects Oncology Fund sponsors the award, which is a critical source of pre-seed capital in the province for early-stage, proof-of-concept projects with commercial potential.
OICR News recently asked Fakir about the story behind his innovation, and what’s next for the RadioSphere.
How did the idea for the RadioSphere come about?
As a medical physicist, I am deeply involved in planning and delivering radiosurgery treatments. I have seen the challenges that patients endure during lengthy and demanding treatment sessions, and I recognize the significant staffing and technological resources this technique demands.
While there are several excellent radiotherapy technologies out there that work well in certain situations, none of them were designed for the complex challenges we’re facing today. We regularly see patients with multiple tumours – some big, some small. Offering them optimal and safe treatments that enhance their chances of controlling the disease while maintaining a good quality of life can be extremely complex.
I wanted to design something more flexible that addresses modern radiosurgery requirements and makes treatments quicker and more comfortable for patients. I initially discussed the idea with Dr. Glenn Bauman (radiation oncologist) and Dr. Jerry Battista (medical physicist), who not only validated the need and the machine concept but also played a crucial role in kickstarting the project.
What makes the RadioSphere unique?
The RadioSphere will allow treating brain tumours of different shapes, sizes and locations with minimal risk of damage to surrounding tissue and therefore minimal risk of side effects. It will also reduce the time of treatment significantly.
What’s also unique is that the RadioSphere can potentially treat other parts of the body – not just the brain. That was important to me because that versatility could help radiotherapy centres become more efficient across a wider range of tumour situations.
What are the next steps for this work?
Our next step is to validate the system design. We’ve confirmed there is a clear clinical need, and now we need to run simulations and design experiments to see how it works in practice. We’re hoping to connect with other healthcare organizations across Ontario who do radiosurgery as part of that validation process.
Ultimately, we want to advance RadioSphere as an Ontario-born and Ontario-led innovation in radiosurgery.
What do you hope this technology could do for patients?
My goal is to provide the technical support that enables clinicians to offer patients the most optimal, safe, and state-of-the-art treatments. These treatments should be more tolerable, more effective, and enhance the overall patient experience, ultimately improving their quality of life.
I also hope that RadioSphere can improve access to radiosurgery. Since it can treat various types of tumours in the brain and other parts of the body, it could be more cost-effective for hospitals. This could enable more patients across Ontario and globally to access precision radiosurgery.
How was the experience of pitching at Falcons’ Fortunes, and how will this award help you and your work with the RadioSphere?
Participating in Falcons’ Fortunes was an invaluable learning experience that seamlessly integrated clinical practice and research with entrepreneurship and commercialization strategy. Preparing and delivering our pitch sharpened our focus on the translational aspects of our work and the process of turning our vision into a tangible product to benefit patients. FACIT’s support during this phase was indispensable, making the effort truly worthwhile through the knowledge we gained.
Falcons’ Fortunes offered a rich environment for networking and new growth opportunities. It provided essential funding to kickstart the project at a critical early stage. It also helped validate the vision behind our product.
Landmark trial brings genomic testing to thousands of Ontarians with cancer
The Ontario-wide Cancer Targeted Nucleic Acid Evaluation (OCTANE) expanded the province’s capacity for next-generation sequencing to deliver personalized approaches to treat cancer
Maddi was just 33 years old when she learned that her breast cancer had metastasized.
She was told the standard-of-care treatment for metastatic breast cancer at the time in 2019 could help manage her symptoms and slow her cancer’s progression, but ultimately her disease was considered terminal.
“I was really in shock,” recalls Maddi, who had already undergone chemotherapy and surgery. “I hadn’t fully understood that my breast cancer could spread like that.”
With the encouragement of a family member, she talked to her Medical Oncologist at the Princess Margaret Cancer Centre (University Health Network), Dr. Philippe Bedard, about options for genomic testing. Sequencing the genome of a tumour is a powerful way to identify ‘biomarkers’, which are molecular clues about the best way to treat a particular tumour.
At the time, Bedard was co-leading the groundbreaking Ontario-wide Cancer Targeted Nucleic Acid Evaluation (OCTANE) clinical trial. Funded by OICR and Princess Margaret and co-led by Bedard’s colleague Dr. Lillian Siu, OCTANE aimed to bring these powerful genomic tests to Ontarians with cancer.
Through OCTANE, Maddi found out her cancer had a particular genetic mutation, and there was another clinical trial testing a therapy that targeted cancers with that exact mutation. This kind of targeted approach to treating cancer is often called ‘personalized medicine’.
She started taking this targeted drug alongside standard-of-care medicines in the summer of 2019 and her tumours responded almost immediately. Today, she has no signs of disease progression, and lives a mostly normal life.
“I’m so grateful I had access to this opportunity,” says Maddi. “It has been life-changing, life-preserving and life-enhancing for me.”
The road to personalized medicine revolution
When Bedard started as a Medical Oncologist about 15 years ago, personalized medicine for cancer was just in its infancy.
There were few known molecular biomarkers, and few drugs to target them.
The technology to sequence tumour genomes was often expensive and cumbersome, and integrating it into clinical care seemed daunting.
“I think back to patients from that time, and I wish they could have benefitted from more personalized, targeted approaches to treating their cancer,” says Bedard.
A decade-and-a-half later, genome sequencing and personalized approaches to cancer care are becoming much more commonplace, and Ontario has positioned itself at the centre of a global revolution in personalized oncology.
While faster, cheaper sequencing technologies are a big reason for the shift, it was also fuelled by OCTANE.
The trial has connected more than 4,338 Ontarians across seven different cancer centres with next-generation sequencing (NGS), leading many participants like Maddi to receive treatments tailored to their tumour’s unique biology.
And while there is still plenty of work ahead to fully realize this revolution, the network OCTANE has built and the wealth of evidence it generated are bringing the future of personalized oncology within reach.
Collaborating to build Ontario capacity
OCTANE was launched in 2016 with a mission to expand NGS testing for advanced solid tumours in Ontario, in the hopes it could connect patients with personalized treatment approaches.
At the time, many Ontario hospitals didn’t have much experience with genomic testing. So Bedard and colleagues worked with clinicians and labs at cancer centres in Toronto, Kingston, London, Hamilton and Ottawa to build out local capacity.
“Before OCTANE, this kind of testing wasn’t feasible in some labs,” Bedard says. “Now, many of them are doing it routinely.”
The trial’s other main goal was to collect patient samples and make the data available to researchers looking to study potential biomarkers and treatments. The more than 3,000 tumour samples and 4,300 blood samples collected by OCTANE have been harnessed for all sorts of new discoveries, including OICR’s groundbreaking new test to find traces of cancer in blood.
OCTANE’s success has largely been driven by its diverse team of experts – including more than three dozen investigators – and its Ontario-wide approach. As the province’s cancer research institute, OICR has helped OCTANE make links between clinicians and researchers across Ontario and provided key infrastructure for the trial. OICR’s Genomics lab has performed much of the genomic sequencing for the study, while OICR Diagnostic Development’s Tissue Portal hosts the study’s samples.
“It’s unique that we can have different cancer centres working together, with support from OICR, to do these types of studies,” Bedard says. “You won’t see that kind of collaboration happen everywhere else.”
Lessons from a unique evaluation
While OCTANE’s primary focus was building capacity for NGS and testing its feasibility in cancer care, the study’s design also allowed for a unique evaluation of how NGS impacted patient outcomes and the health system at large.
Consenting OCTANE participants provided their Ontario health card number so their health outcomes could be followed through healthcare administrative data.
“This was a great success because we were able to answer the questions we wanted for a much lower cost than if we had to collect all of this information directly from thousands of patients over the course of many years,” says Dr. Timothy Hanna, a Clinician Scientist with OICR and the Division of Cancer Care and Epidemiology at Queen’s University
Their analysis was recently published in the Lancet journal EClinicalMedicine. It showed that cancer patients who had NGS through OCTANE were more than twice as likely to enroll in a clinical trial. Though NGS caused healthcare spending per-patient to rise, publicly funded drug costs decreased.
Perhaps their most significant finding was that NGS was not associated with an increase in overall survival in OCTANE participants. People with some cancer types – including ovary and biliary tract – survived longer after having genomic testing, but this difference was not seen in other cancers such as colon and breast cancer.
While this was not the result OCTANE researchers were hoping for, the findings point to several explanations and lessons to take forward. For example, only about four per cent of OCTANE participants received a targeted therapy, despite 54 per cent being found to have at least one actionable biomarker.
Hanna says this can partly be explained by the lack of a defined ‘pathway’ to connect cancer patients with personalized medicine clinical trials. It often falls on researchers and patients to parse through all available trial options and their unique eligibility criteria and compare that against patients’ health history and genomic profile. And this was even more challenging five years ago when OCTANE patients were recruited.
Thankfully this is a problem OCTANE data is being harnessed to help overcome, as OICR and Princess Margaret researchers work to develop machine learning software that links patients with cancer clinical trials.
Doubling down on personalized oncology research
Bedard says OCTANE results also reinforce the need to double down on genomic research to identify more biomarkers and understand how they can be used to guide treatment. With the recent launch of OCTANE 2.0, Bedard and Princess Margaret’s Dr. Benjamin Haibe-Kains are doing just that.
OCTANE 2.0 will build upon the network established in the first trial and focus more on treatment response and resistance. Bedard, Haibe-Kains and colleagues will use NGS to monitor how patients respond to certain drugs and identify people who have a high risk of relapse so they can be treated with a different approach.
The trial will put an extra emphasis on sequencing blood samples, looking for tiny fragments of tumour DNA that can give clues on the progress of a patient’s disease.
Bedard says he hopes OCTANE 2.0 will help generate new tools and therapies, and further strengthen Ontario’s capacity for personalized medicine.
“The technology is moving fast, and the network we’ve built in Ontario is making great progress,” says Bedard. “I’m enthusiastic this will translate into significant benefits for patients, helping them live longer, live better, and potentially be cured of cancer.”
Looking at a brighter future
Maddi hesitates when talking about approaching the all-important five-year mark since starting her combination of therapies. She’s just grateful to be living well and feeling well, aside from some manageable side effects from her medications.
It’s dramatically different from where she expected to be when she was first diagnosed with metastatic disease.
“This research has granted me five years of essentially stable health,” she says. “I want it to be available to more people, and I want them to know there’s hope.”
Maddi’s full name has not been used in order to protect her privacy.
Ask a Cancer Researcher: Why is it so challenging to find a cure for cancer?
In our latest Ask a Cancer Researcher video, Dr. Lincoln Stein explains why cancer is so difficult to cure, the progress that has been made and what OICR is doing to help cancer patients live longer and better lives.
New 3CTN initiative aims to address barriers faced by underrepresented populations and expand clinical trial involvement
Clinical trials lead to new and better ways of diagnosing and treating those with cancer. They also provide an opportunity for interested patients to access potentially life-changing care within a trial. However, some patients may be unable to participate in trials due to other health issues, family and work limitations, costs related to time or travel, or other concerns about participating in research. This can limit understanding of how new treatments will work in all those that may be offered them in the future.
To help improve equity, diversity and inclusion in all aspects of clinical trials conduct, the Canadian Cancer Clinical Trials Network (3CTN) launched a framework and tool kit that provide recommendations and links to relevant resources. These new resources were developed with expert stakeholders from across Canada including clinical research professionals, trial sponsors, and people with lived experience. Included were individuals of historically underrepresented communities such as our geriatric population (70+), adolescents and young adults, those living outside urban areas, immigrants/newcomers to Canada, Indigenous peoples (First Nations, Métis and Inuit), racialized individuals, and members of the sexual and gender diverse community.
“For many people with cancer, clinical trials offer hope and a way to help shape the future of cancer care. There is no group of people that cancer does not touch, therefore it is critically important that this future is informed by a diverse range of experiences,” says Michelle Audoin, a patient partner involved in the development of the framework and toolkit. “I am proud of the collaborative effort to develop these new resources and am excited to see them being deployed across Canada.”
The framework and toolkit were developed as living documents, providing the opportunity for others working in clinical trials to review and contribute to the content as evidence and experiences evolve with time. To this end, 3CTN and its partners will carry out periodic reviews to ensure the materials are up to date and reflect changes in best practices.
“These resources provide us with a solid foundation on which to build a truly equitable, diverse and inclusive clinical trial ecosystem in Canada,” says Dr. Janet Dancey, 3CTN Scientific Director. “I extend my heartfelt thanks to all of our partners who contributed to the development of these vital tools.”
Help us shape OICR’s next five year strategic plan
OICR is developing its 2026-2031 Strategic Plan and we want to hear from you!
By completing this short survey you can help inform the direction of the Institute’s research and initiatives. We value the feedback of all, including those with cancer and their families, researchers, clinicians and all those with an interest in cancer research in Ontario.
If you’d like to know more about OICR’s recent activities, our current strategic plan and latest impact report can be viewed here. Responses are anonymous. If you have any questions or comments about the strategic planning process, please email Paula Neves at pneves@oicr.on.ca.
Ask a Cancer Researcher: How can ultrasound be used to detect breast cancer?
OICR patient partner Vivian Simbul Sim talks to Amal Aziz, a researcher and master’s student working within the lab of Dr. Aaron Fenster, about the various methods that can be used to screen for breast cancer in women with dense breasts.
These women often need additional imaging after a standard mammogram. Aziz explains how a new 3D ultrasound technology that she is developing with her colleagues can deliver this screening in a more accessible manner than MRIs.
A message from the President and Scientific Director on the passing of Andrea Redway
Today I am writing to share the sad news of the passing of Andrea Redway, who served admirably as a patient representative on OICR’s Board of Directors and as a patient partner on an OICR Window-of-Opportunity Network clinical trial.
Andrea brought her skills and experience as a lawyer and her passion for advocacy to the Board and helped the organization maintain its focus on the most important aspect of our work – those with cancer. Andrea was sharp-minded and knowledgeable but also apparent was her kind, calm and empathetic demeanor. She will be missed by those of us at OICR who had the pleasure of working with her as well as many others within the Canadian cancer research community.
Andrea was diagnosed with Stage 4 lung cancer in 2015 and was subsequently treated with immunotherapy, which was novel at the time. This experience provided her with a deep personal understanding of the significance of cancer research. This compelled Andrea to direct her energy into pushing for improvements in cancer research and care. She was also involved in patient support and education initiatives. In addition to OICR, Andrea worked with Lung Cancer Canada, the Canadian Cancer Survivors’ Network, The Ottawa Hospital, the Canadian Cancer Society, Merck Canada, RETpositive and the Happy Lungs Project.
While today the news is of Andrea’s death, it is through her life that she made a remarkable impact on cancer research and those around her. I know that the OICR community will be forever grateful for her contributions and that future generations will benefit from her legacy. On behalf of OICR I extend our deepest condolences to Andrea’s family, friends and colleagues.
Dr. Laszlo Radvanyi
President and Scientific Director
OICR
How two cancers make themselves harder to treat by suppressing the immune system
New research shows that prostate cancer and Ewing sarcoma exploit a biological process to their advantage.
An international study co-led by OICR researchers has demonstrated how two forms of cancer work to suppress the immune system and could inform new ways to diagnose and treat the diseases.
In their study, published in the Journal of Clinical Investigation, researchers from Ontario, British Colombia and Europe looked at prostate cancer and Ewing sarcoma – a rare cancer of the bones and soft tissue that affects children most often – and identified a novel mechanism that contributes to the growth of both types of cancer and help them cause abnormalities in a patient’s immune system.
The team found that Ewing sarcoma and prostate cancer cells release ‘extracellular vesicles’ that can cause inflammation and DNA damage in the non-cancerous cells surrounding a tumour and ultimately lead to the suppression of a patient’s immune system.
These extracellular vesicles can also be taken up across the body by immune system cells, causing them to release ‘pro-inflammatory cytokines’ that help drive tumour growth and suppress immune responses that can help fight cancer.
“Our findings reveal a new biological pathway by which tumour cells are able to dampen and evade the body’s immune system,” says Dr. Lincoln Stein, Head of Adaptive Oncology at OICR and one of the paper’s senior authors. “This raises the possibility of developing diagnostic tests based on these insights to determine which patients are likely to benefit from immunotherapy. In the future, we may also be able to develop drugs that reverse the immune-evasion pathway identified in this study.”
The team went on to examine how exactly these extracellular vesicles work to drive tumours and suppress the immune system. They found a novel mechanism involving the expression of ‘non-coding DNA’, which makes up the bulk of our genome but is only now being linked with cancer. This part of the genome has been known as the ‘dark genome’.
One of the key findings was that the DNA and RNA sequences from the non-coding elements of Ewing sarcoma and some prostate cancer cells mimic sequences expressed by viruses and other pathogens. In fact, they ‘infect’ normal cells by tricking them into thinking they are being infected by a virus, generating a persistent inflammatory response that supresses rather than actives the immune system.
They also found that the uptake of these extracellular vesicles in normal immune cells in the blood can leave a “footprint” in cells that can be identified and measured as a novel approach to detect cancer. They hope this discovery could lead to new tools to detect, monitor and treat the disease.
“This study shows the power of collaborative science, allowing us to uncover a really complex process showing how tumour cells exploit ancient biology to their advantage, which we can then hopefully use for diagnostic and therapeutic purposes,” says Dr. Poul Sorensen, a distinguished scientist at the BC Cancer Research Institute and Professor of Pathology at the University of British Columbia and another of the study’s senior authors.
The research was also co-led by Dr. Laszlo Radvanyi (co-senior author), President and Scientific Director of OICR, whose team included Dr. Peter Ruzanov and Dr. Valentina Evdokimova as lead authors.
This story was adapted in part from an article by BC Cancer.
‘Smart people’ working to make a difference: Co-op student reflects on OICR conference
McMaster University biochemistry student Suky Zheng attended OICR’s 2024 Translational Research conference and was inspired by the people she met and their efforts to help people affected by cancer.
It has been said that if you’re the smartest person in the room, then you’re in the wrong room.
As one of the youngest attendees at the biennial OICR Translational Research Conference, I can attest that there were a lot of smart people in the room. About 250 of Ontario and Canada’s top cancer researchers, students and trainees gathered together to share their work and discuss some of the most recent advances in cancer detection, therapeutics and diagnostic strategies.
Topics included everything from new cancer targets to powerful imaging and sequencing technology, to the exciting potential of liquid biopsies. Speakers also discussed how AI and machine learning can be harnessed for precision medicine and how to improve clinical trials to better meet patient needs. This year’s conference program gave attendees a panoramic view of all the cutting-edge research work that makes Ontario one of the best places for cancer care in the country.
Through my two days at the TRC, I watched incredible presentations and lively discussions from all sorts of experts, including two phenomenal keynotes from Dr. George Kassiotis (Francis Crick Institute, London UK), and Dr. Daphne Koller (CEO of Insitro). However, one of the main highlights for me was getting to hear from all of our patient partners, and learning about how OICR works with its partner, FACIT, to commercialize research so that scientific innovations can flourish in Ontario. OICR is truly unique for how it engages patients in all aspects of research, and for how it emphasizes bringing research from the lab into the clinic so that it can benefit those who need it most.
A very big shout-out to the conference organizing committee for such an unforgettable and memorable experience! I had the privilege of presenting some of our research with my co-presenter Minsheng Hung, another research student working with me in Dr. Laszlo Radvanyi’s lab. We were very honoured to have our poster win a presentation award as well. Being that this is my very first time attending an in-person conference, this memory will definitely be extra special.
Many of my colleagues and bosses still smile a little and tease at my bright-eyed ‘newbie’ attitude, since I get excited over basically anything and everything. But I have to say, isn’t this all so worth being excited for?
While being in a room full of smart people will always feel intimidating, it is also what continues to fuel my passion for science and ambition to strive in becoming a better researcher. So, a huge thank you to all the smart people I met last week — you have opened up my eyes to what it means to bring research to life.
Suky Zheng is a student in McMaster University’s Honours Bachelor of Health Sciences in Biochemistry and Biomedical Sciences program, and a research co-op student in Dr. Laszlo Radvanyi’s immuno-oncology lab at OICR.