New “window-of-opportunity” clinical trials explore cutting-edge treatments for cancers of the liver, head and neck

Two new studies join the Ontario Institute for Cancer Research (OICR) portfolio of Window-of-Opportunity (WOO) Network clinical trials.

April 18, 2024, TORONTO – A new round of clinical trials supported by the Ontario Institute for Cancer Research (OICR) will harness a unique opportunity to test some of the newest treatment strategies for a range of different cancers.

OICR has announced two new clinical trials as part of its Window-of-Opportunity (WOO) Network, which brings together Ontario researchers, clinicians and patients to study the biology of newly diagnosed and recurrent tumours.

“‘Window-of-opportunity’ clinical trials take advantage of the two-to-eight-week period between the diagnosis of cancer and the surgery to remove the cancer, at a time when no treatment is happening,” says Surgical Oncologist, OICR Associate Scientist, and WOO Network Co-lead Dr. Angel Arnaout. “WOO Network trials capitalize on this window to study the biological effect of new cancer treatments without delaying or altering a patient’s primary treatment strategy.”

“Testing cancer therapies during this window of time allows us to understand and measure how they work against the tumour, and we’re very grateful to patients who participate in these studies and provide us this exceptional opportunity,” says WOO Network Co-lead Dr. Melanie Spears, who is also a Principal Research Scientist at OICR and Co-Director of the Institute’s Diagnostic Development program.

These latest WOO Network trials focus on liver cancer and head and neck cancers, and seek to understand how immunotherapies work alongside other innovative treatments to prepare a patient’s immune system to fight cancer. They will both also look for biological clues called ‘biomarkers’ that could indicate which patients would benefit most from different treatments.

Dr. Sara Kuruvilla and Dr. Anthony Nichols of the London Regional Cancer Program at London Health Sciences Centre (LHSC) and Lawson Health Research Institute will investigate the effectiveness of a novel immunotherapy drug combination before surgery to remove head and neck tumours, including monitoring how patients’ immune systems respond and if they experience fewer side effects from surgery. Findings are expected to provide preliminary evidence to support further evaluation of this approach in larger clinical trials.

“Recurrence is common after surgery for mouth and throat cancers, and surgical treatment can severely impact patients’ quality of life. We hope that receiving immunotherapy before surgery can improve a patient’s immune response, improve their outcomes and reduce the side effects they face.” – Dr. Sara Kuruvilla, Medical Oncologist at LHSC, Associate Scientist at Lawson, and Associate Professor of Oncology at Western University’s Schulich School of Medicine & Dentistry

Dr. Pablo Serrano and Dr. Brandon Meyers of Hamilton Health Sciences and McMaster University will study how a common immunotherapy (Durvalumab) impacts liver tumours after patients have stereotactic body radiation therapy (SBRT) but before they have surgery, with hopes that the combination strengthens patients’ immune systems to fight cancer.

“We aim to see if the combination of immunotherapy and radiation therapy can increase the number of immune cells that attack cancer, reduce the number of immune cells that allow cancer to grow, and potentially improve the prognosis of patients with liver cancer.” – Dr. Pablo Serrano, Scientist at Escarpment Cancer Research Institute (Hamilton Health Sciences and McMaster University) and Associate Professor of Surgery at McMaster University

These new clinical trials join OICR’s existing portfolio of WOO Network trials, which explore various therapeutic approaches and the impact they have on immune response in patients with a variety of cancers including lung, breast, pancreatic and bladder cancers.

OICR created the WOO Network in 2020 to help build Ontario’s capacity for state-of-the-art clinical trials by funding studies, mentoring new investigators and connecting scientists, clinicians, patient and industry partners.

“OICR’s WOO Network is a landmark program that leverages our capabilities in genomics and biomarker discovery to improve the drug development paradigm and better understand how new therapies work,” says OICR President and Scientific Director Dr. Laszlo Radvanyi. “In its third year of operation, the network is already yielding important insights about different types of cancers and the best ways to treat them. These newest trials will drive even more innovations to treat cancer more precisely and give patients the best chance at longer, healthier lives.”

“The Ontario government is proud to support new discoveries and innovations in cancer research by funding the work of OICR,” said Jill Dunlop, Minister of Colleges and Universities. “New clinical trials are key to testing therapies that have real-life impacts for patients in Ontario, ultimately helping them lead longer and healthier lives.”

About OICR
OICR is funded by the Government of Ontario. As the province’s cancer research institute, we take on the biggest challenges in cancer research and deliver real-world solutions to find cancer earlier and treat it more effectively. We are committed to helping people living with cancer, as well as future generations, live longer and healthier lives. For more information visit http://www.oicr.on.ca.

The views expressed are those of OICR and do not necessarily reflect the views of the Province of Ontario.

Ontario cancer community comes together at OICR Translational Research Conference

Scientists, clinicians and patients shared their achievements and ideas for improving the lives of people affected by cancer.

For a moment, on stage in front of a crowd of accomplished cancer researchers from Ontario and beyond, Carla Bossart-Pletzer wondered if she belonged.

A designer and illustrator by trade, Bossart-Pletzer was serving as MC for OICR’s 2024 Translational Research Conference, a gathering of about 250 people from across OICR’s vast cancer research network.

“Then I remembered what my accomplishment is,” Bossart-Pletzer told the crowd. “My accomplishment is that I’m alive to be here – I’m surviving cancer.”

She said that her diagnosis of inflammatory triple negative breast cancer may have been a death sentence, if not for recent advances by cancer researchers.

“Thank you for what you’ve done and continue to do to give people like me a chance,” said Bossart-Pletzer, who has herself become a key contributor to cancer research as a member of OICR’s Patient and Family Advisory Council.

Bossart-Pletzer’s introduction set the tone the two-day conference – held March 26-27 in King City, Ont. – which showcased scientific innovations across many different disciplines, but was singularly focused on improving the lives of people affected by cancer.

The research presented at the conference took different approaches towards that goal. Some sessions covered new technologies for screening, diagnosing, monitoring and treating cancers, like liquid biopsy and novel targets for cancer drugs. Others focused on how to make research more accessible to diverse groups of people, and how to make sure promising research discoveries are implemented in the health system, where they can make a difference for patients.

The event was bookended by two impressive keynote speakers: Dr. George Kassiotis, a leading retroviral immunity researcher at The Francis Crick Institute, and Daphne Koller, CEO and founder of machine-learning driven drug discovery company insitro. And all conference sessions were co-facilitated by a person with lived experience of cancer, who helped to put the science into perspective.

The conference also put a spotlight on the next generation of scientists, including graduate students, postdoctoral fellows and early career researchers. Awards were handed out to the most exciting poster presentations by student researchers, including awards from the Ontario Rising Stars in Cancer Research Network and the new Acorn-2-Oak Commercialization Award from FACIT.

In his closing remarks, OICR President and Scientific Director Dr. Laszlo Radvanyi said the diversity of research presented at the conference is a testament to the infrastructure OICR has built. In addition to conducting and funding cutting-edge cancer research across the province, the Institute has helped make Ontario a global leader in genomics, liquid biopsy, genome informatics, artificial intelligence, radiopharmaceuticals, and other critical areas of cancer research.

“OICR is moving in the right direction. Let’s keep it up.”
Dr. Laszlo Radvanyi

PFAC Chair Terry Hawrysh applauded OICR’s emphasis on enabling early detection and intervention, while improving quality of life and reducing toxicities – outcomes he says matter to patients. He was also encouraged to see researchers focused on delivering these outcomes in an equitable and accessible manner.

“OICR is keyed in on the right things,” Hawrysh said. “I am walking away from this conference encouraged, with hope intact, and ready to roll up my sleeves and continue to work alongside you.”

FDA approves first cell therapy in landmark achievement for personalized medicine

OICR President and Scientific Director Dr. Laszlo Radvanyi reflects on the potential impact of a novel drug for metastatic melanoma, and his important role in the drug’s development.

The U.S. Food and Drug Administration (FDA) has granted accelerated approval to a first-of-its-kind therapy that harnesses a patient’s own immune cells to fight skin cancer.

The drug, known as lifileucel (or Amtagvi^TM), is made by extracting cells called ‘tumour infiltrating lymphocytes’ (TIL) from a patient’s tumour sample and then using them to kill that same tumour.

The FDA approved lifileucel for patients with metastatic melanoma whose cancer could not be stopped by other treatments, making it the first TIL therapy approved for commercial use in North America. It also marks a significant achievement for Iovance Biotherapeutics, the U.S. biotech company behind it.

OICR President and Scientific Director Dr. Laszlo Radvanyi was Iovance’s founding Chief Scientific Officer (CSO) in 2014 and 2015 when it was initially established as Lion Biotechnologies. He and his team, together with then CEO Manish Singh, designed and built the company’s lab-office complex in Florida, recruited its initial scientists and lab technicians, and did the complex pre-clinical development work for Iovance’s first critical lifileucel trials in melanoma.

OICR News asked Radvanyi about the work that went into this groundbreaking therapy and what its FDA approval means for patients with melanoma and other cancers.

Why is this such an exciting development for patients with metastatic melanoma?

In this new era of personalized medicine, TIL therapy is about as personalized as it gets. It is made from a person’s own T cells, which are extracted, ‘expanded’ and infused back into the patient to kill the very tumour they came from.

The data from Iovance’s clinical trials has been tremendously exciting. Many people have had complete response after TIL therapy, meaning their cancer is completely gone. It is truly a life-saving therapy, and it will help make metastatic melanoma a survivable disease.

How significant is this achievement from a scientific perspective?

People have been trying to get a cell therapy to market for about 30 years, and they have generally been considered extremely difficult to commercialize. That’s because it’s a very difficult, involved process to manufacture cell therapies, and it can be time-consuming and costly.

When I helped launch Iovance as founding CSO, many people balked at the idea of advancing cell therapy and getting it approved by the FDA.

Well, we took up that challenge and did a huge amount of work to prove that it was safe and effective for patients and reduce the associated time and costs. My colleagues at Iovance and I showed that with hard work and creativity, we can do something no one thought could be achieved, and something that will make a major impact on the lives of people with cancer.

Does the approval of the first TIL therapy have implications beyond melanoma?

While this FDA approval is for metastatic melanoma, TIL therapy has the potential to be applied to all sorts of other tumour types. There are ongoing clinical trials for lung cancer, breast cancer, ovarian cancer and pancreatic cancer.

In my own lab at OICR, we are working to understand all the different antigens that trigger TILs to attack tumours. We’re exploring whether TILs recognize what are called ‘non-coding antigens’, which are considered great targets for cancer therapies. If so, that could open the potential for all sorts of other personalized TIL drugs.

What’s the status of TIL therapies in Canada?

While TIL therapies have not yet been approved for commercial use by Health Canada, I would love to see Canada approve this life-saving therapy as well as develop TIL manufacturing capacity in the future. Ironically, several Canadian scientists – including myself – were involved first-hand in establishing Iovance in 2014-2016 and laying the groundwork for the company’s success.

Canada also has many visionary leaders in the TIL field. This includes Dr. Pamela Ohashi and Dr. Marcus Butler at Princess Margaret Cancer Centre, who have been treating patients with TIL therapy as part of clinical trials. Dr. Simon Turcotte at the Centre Hospitalier de l’Université de Montréal has been active in establishing TIL manufacturing and clinical trials for melanoma and other cancers, while Drs. Brad Nelson and Robert Holt of BC Cancer have also been developing TIL therapy. Canadian biotech company Turnstone Biologics has also gotten into the TIL space through the acquisition of a California biotech, Myst Therapeutics, in 2021.

All this attests to our talent and capacity to be a significant player in the growing TIL therapy field in Canada. And there’s no reason why Canadians cannot use our own biomanufacturing expertise to advance and commercialize TIL therapies, like we did with an OICR-supported platform to manufacture CAR-T cell therapy in Canada through a consortium called BioCanRx.

As founding CSO of Iovance, I’m proud to have helped set things in motion for FDA approval, and proud of my colleagues there for realizing this landmark achievement. Now, as President and Scientific Director of OICR, I am excited to continue building capacity in Ontario and across Canada to develop novel therapies and get them patients who need them.

Do anxiety and depression affect our risk of cancer?

An international research project used Ontario Health Study data to investigate possible links between depression, anxiety and certain cancers.

Living with depression and anxiety has been thought to put people at a higher risk for certain cancers. New research from a large international study, which includes data from thousands of Ontario Health Study (OHS) participants, is showing otherwise.

In a recent paper published in the journal Cancer, the PSY-CA (PSYchosocial factors and CAncer incidence) project failed to demonstrate an association between depression and anxiety and breast, prostate, colorectal, and alcohol-related cancers, or cancers overall. However, it did find an association of depression and anxiety (both symptoms and diagnoses) with the incidence of lung cancer and smoking-related cancers. The paper noted that those associations were substantially reduced when adjusted for the presence of other known risk factors for lung cancers, such as smoking, alcohol use, and body mass index.

The PSY-CA Consortium is examining data from 18 study populations in the Netherlands, United Kingdom, Norway and Canada. Using information from cancer registries, this meta-analysis (a statistical analysis of multiple studies) looked at data collected from more than 300,000 adults to explore the relationship between specific psychosocial factors and a cancer diagnosis.

Dr. David Soave

Dr. David Soave of Wilfrid Laurier University led the OHS-related analysis for the PSY-CA project. He looked at data from 14,384 OHS participants. Other researchers looked at data from participants in two sister cohorts of the OHS, Atlantic PATH and CARTaGENE in Quebec.

He indicated the Ontario Health Study cohort of participants was well suited for the international project, as there was a substantial amount of information available on psychosocial factors that could be linked to known cancer diagnoses in the OHS study population.

OHS, which is hosted by OICR, is an ongoing research study involving more than 225,000 Ontario residents who are making their personal health information available to researchers.

The psychosocial factors explored in the study were:

Diagnosed depression
Diagnosed anxiety disorder and anxiety symptoms
Recent loss of a close family member or partner
Perceived low social support
Relationship status
General distress
Neuroticism

What should people take away from the study?

“Our results may be informative to many patients with cancer who believe their diagnosis is attributed to previous anxiety or depression,” said Soave.

He noted further research is still needed to understand how depression, anxiety, health behaviours and lung cancer are related.

***

This article was written by the Ontario Health Study and shared with permission. The original article is published at ontariohealthstudy.ca

National conference helps OICR PhD students shape their research and their futures

Several OICR-based PhD candidates were able to share their research at the 2023 Canadian Cancer Research Conference.

Surrounded by cancer patients, clinicians and hundreds of the brightest minds in Canadian cancer research, Rhea Ahluwalia felt a part of something bigger.

Ahluwalia was one of several OICR-based scientists and PhD students to travel to the 2023 Canadian Cancer Research Conference (CCRC) in Halifax. She says the people she met at the conference and the diversity of their perspectives helped her see beyond her own research “bubble.”

“I got to see the bigger picture, and how all of our work is like different cogs that keep the machine of cancer research moving forward to help patients,” says Ahluwalia, a University of Toronto PhD student based in Dr. Lincoln Stein’s lab at OICR. “It was really inspiring and made my work feel even more worthwhile.”

Ahluwalia shared her research, which involves using computational methods to understand the biology of neuroblastoma, as part of the CCRC poster sessions. She also gave a presentation during of one the conference’s sessions on paediatric cancers.

She says discussing her PhD project with colleagues across Canada was helpful to her current research as well as her future ambitions.

“I met and spoke with people from many different fields,” she says. “As a student, that helps me see what I could be looking at as a career in the future.”

CCRC is a biennial conference run by the Canadian Cancer Research Alliance. This year’s conference was held in-person for the first time since before the COVID-19 pandemic, and OICR was well represented. Dr. Trevor Pugh gave one of the opening plenary presentations, while OICR researchers spoke at various sessions throughout the three-day conference.

But the experience was especially invigorating for PhD researchers.

PhD student Farzan Taj – Ahluwalia’s colleague in Stein Lab – says the conference helped him refresh his knowledge on topics like artificial intelligence and learn about the latest innovations in precision oncology.

“The conference was a unique opportunity to interact with other researchers and have stimulating conversations about my work,” says Taj, whose conference poster was about using deep learning tools to predict how cancer cells will respond to treatments.

Stein Lab’s Xindi Zhang says she was inspired hearing from the many cancer patients and family members who attended the conference.

“They ignited my passion to deepen my understanding of cancer research, helped me realize the significance of my role as a research trainee, and motivated me to contribute more to advancing the field,” she says.

Zhang also received some valuable insights from colleagues that may help shape the future of her research project, in which she uses computational methods to classify the site and histology of tumours.

“I think it’s really important to connect with others who share your passion, gain diverse perspectives and contribute to the collective knowledge,” Zhang says.

Study shows that smoking ‘stops’ cancer-fighting proteins, causing cancer and making it harder to treat

In-depth analysis links harmful DNA mutations to tobacco smoking and other causes of cancer.

November 3, TORONTO — Scientists at the Ontario Institute for Cancer Research (OICR) have uncovered one way tobacco smoking causes cancer and makes it harder to treat by undermining the body’s anti-cancer safeguards.

Their new study, published today in Science Advances, links tobacco smoking to harmful changes in DNA called ‘stop-gain mutations’ that tell the body to stop making certain proteins before they are fully formed.

They found that these stop-gain mutations were especially prevalent in genes known as ‘tumour-suppressors’, which make proteins that would normally prevent abnormal cells from growing.

“Our study showed that smoking is associated with changes to DNA that disrupt the formation of tumour suppressors,” says Nina Adler, a University of Toronto PhD student who led the study during her postgraduate research in Dr. Jüri Reimand’s lab at OICR. “Without them, abnormal cells are allowed to keep growing unchecked by the cell’s defenses and cancer can develop more easily.”

Adler, Reimand and colleagues used powerful computational tools to analyze DNA from more than 12,000 tumour samples across 18 different types of cancer. Their analysis showed a strong link between stop-gain mutations in lung cancer and the telltale ‘footprint’ that smoking leaves in DNA.

The researchers then looked at whether how much someone smoked had an impact. Sure enough, their analysis showed that more smoking led to more of these harmful mutations, which can ultimately make cancer more complex and harder to treat.

“Tobacco does a lot of damage to our DNA, and that can have a major impact on the function of our cells,” says Reimand, an OICR Investigator and Associate Professor at the University of Toronto. “Our study highlights how tobacco smoking actually deactivates critical proteins, which are the building blocks of our cells, and the impact that can have on our long-term health.”

The study also identified other factors and processes responsible for creating large numbers of stop-gain mutations, which are also called ‘nonsense’ mutations. Some, like a group of enzymes called APOBEC that is strongly linked to stop-gain mutations in breast cancer and other cancer types, occur naturally in the body. Other factors like unhealthy diet and alcohol consumption are also likely to have similar damaging effects on DNA, but Reimand says more information is needed to fully understand how that works.

As for smoking, Adler says the findings from this study are an important piece of the puzzle behind a leading cause cancer in the world.

“Everyone knows that smoking can cause cancer, but being able to explain one of the ways this works at a molecular level is an important step in understanding how our lifestyle affects our risk of cancer,” Adler says.

OICR President Dr. Laszlo Radvanyi says these new insights should reinforce that tobacco smoking is one of the biggest threats to our health.

“This is further proof of the immense damage smoking has on our bodies, and further evidence that stopping smoking is always the right choice,” Radvanyi says.

OICR is a collaborative, not-for-profit research institute funded by the Government of Ontario. We conduct and enable high-impact translational cancer research to accelerate the development of discoveries for patients around the world while maximizing the economic benefit of this research for the people of Ontario. For more information visit http://www.oicr.on.ca.

The views expressed are those of OICR and do not necessarily reflect the views of the Province of Ontario.

First-ever national library of genomic data will help personalize cancer treatment in Canada and around the world

OICR will be playing a major role in the forthcoming Pan-Canadian Genome Library.

A groundbreaking initiative to unify genomic datasets from across Canada into a national library will drive innovations in personalized treatments for diseases like cancer, and OICR will be a major contributor.

The Canadian Institutes of Health Research (CIHR) announced $15 million in funding to create a Pan-Canadian Genome Library, a first-of-its kind resource for researchers, healthcare professionals and others looking to find and treat diseases more effectively.

The project will build on Canada’s global leadership in genomic research, which until now has been limited by the lack of a national approach to capture, store and access genomic data. This new library will provide a Canada-wide picture of diseases like cancer and the biology behind them, which will lead to new approaches to treating disease that are tailored to a person’s unique biology.

“Canada has several different projects and platforms that collect genomic information and patient data, but we do not have a consolidated infrastructure to connect all this information in an ethical and sustainable way,” says Dr. Mélanie Courtot, a Principal Investigator and Director of Genome Informatics at OICR. “By bringing these large datasets together, we can gain much more information about cancer and other diseases across the whole of the Canadian population.”

Courtot joins OICR’s Head of Adaptive Oncology Dr. Lincoln Stein and Associate Director of Adaptive Oncology Dr. Michelle Brazas in co-leading several key components of the library, including infrastructure, governance and outreach. The project will be led by Dr. Guillaume Bourque, Director of Bioinformatics at the McGill Genome Centre.

Courtot’s Genome Informatics team will leverage their expertise with other major databases like the International Cancer Genome Consortium (ICGC). This work will be supported by Overture, a data management software suite developed by OICR Genome Informatics that is driving genomic research in Canada and around the world.

Landmark study uses OICR Genomics test to find early signs of cancer in blood

Dr. Trevor Pugh talks about his new paper in Cancer Discovery and how it could help transform screening for people with Li Fraumeni Syndrome (LFS).

People with Li Fraumeni Syndrome (LFS) can never really forget about cancer.

Being diagnosed with LFS, a rare genetic condition, comes with a near 100 per cent risk of developing cancer in your lifetime. And because the disease is hereditary, it also means your parents, siblings and children could face the same unfortunate odds.

Targeted cancer screening programs for people with LFS (as set out by the Toronto Protocol) have gone a long way toward catching cancer early and giving them some peace of mind. But the constant testing can be a burden in itself, especially for people live far away from major hospitals. And even an annual combination of tests that includes bloodwork, ultrasounds and a full-body MRI can’t always find cancer as soon as it develops.

That’s why a landmark study by researchers at OICR, UHN and SickKids and funded by the Terry Fox Research Institute has the potential to transform how people with LFS are screened for cancer and give them a better chance at surviving the disease.

In the study, published in Cancer Discovery, researchers were able to find early signs of cancer in blood samples from people with LFS months before cancer was detected by other tests.

The signs they found were tiny fragments of tumour DNA that circulate in the bloodstream called ‘cell-free DNA’. Cell-free DNA from cancer cells is often detectable before the actual tumour is visible. And because they are in the bloodstream, you only need a simple blood sample to find and analyze them, which is easier on the patient than a taking a biopsy or a having a full-body MRI.

“We were able to detect multiple different types of DNA changes in blood that were a telltale sign that cancer was developing somewhere in the body,” Dr. Trevor Pugh, Senior Scientist at and Director of OICR Genomics, said in a news release.

Pugh co-led the study with Dr. David Malkin (SickKids) and Dr. Raymond Kim (UHN and the Ontario Hereditary Cancer Research Network). He also oversaw the genetic testing and analysis, which was conducted by the OICR Genomics Program.

OICR News recently sat down with Pugh to discuss this work, what it could mean for people with LFS, and what happens next.

How did you first get involved in this project?

That began many years ago when I first met Raymond Kim from Princess Margaret and David Malkin from SickKids, who are frontline geneticists working directly with patients who have LFS and innovators in the world of clinical genetics.

What resonated with me in speaking to them was the experience of families with LFS. They undergo a huge amount of surveillance to try and find cancer, which is extremely important but can be challenging for them. Many families having to travel long distances and sometimes stay in Toronto for multiple days in a row and get tested.

At the same time, the technology to test blood for signs of cancer – sometimes called ‘liquid biopsies’ – was advancing. So, we wondered what impact liquid biopsies could have on people and families that undergo such intense cancer surveillance.

What did you find as part of this study?
We looked back at blood samples from people with LFS that were taken as part of their regular surveillance.

We first looked at people whose other tests showed they had developed cancer. Sure enough, most of their blood samples tested positive for cell-free DNA. Then we looked at people whose surveillance gave them a clean bill of health. Just over a third of those patients also had signs of cancer in their blood.

So, we had inkling is that what we’re detecting in their blood are the earliest signs of cancer that don’t get picked by other kinds of testing. This was now an opportunity to start combining our molecular data with imaging to see what kind of lead time we were getting.

What’s the next step in this work?
The next step is a clinical prospective study where we’ll try to answer the question “so what?”

In contrast to our past work, we will now be testing cell-free DNA more frequently, every four months, and delivering results back to the managing physicians and their patients. If we see a cancer signal, we will confirm the finding with a clinic visit similar to their regular annual surveillance. This will show us whether we can actually find cancer earlier than the current annual surveillance approach and inform what we can do with that information to help people get treated as quickly and effectively as possible.

This is the really exciting part of the work where we move from retrospective mode, where history is already written, into prospective mode where we can put our results into practice. This new project brought together a big multidisciplinary team, including multiple patient advocates, to roll this trial out across the country.

How could you see liquid biopsies changing the way people with LFS are screened?

As my colleagues and I wrote in another recent journal article, liquid biopsies have the potential to shift the paradigm in surveillance for people with LFS and other hereditary cancer syndromes.

If we get positive findings from our upcoming trial, I could see blood tests ultimately being added to surveillance protocols in between other more intense testing. Then, if the blood test is positive for cell-free DNA, it could be the ‘canary in the coal mine’ that triggers a full screening.

This could go a long way in easing the anxiety that comes with having LFS and knowing you’ll likely develop cancer at some point. It also could improve access to cancer screening for people who live outside of larger cities, because a blood test can be taken just about anywhere.

What was OICR Genomics’ role in the study?

OICR Genomics is the backbone that supported this major collaboration. We worked closely with partners to develop blood biopsy technology that fit the unique needs of the study, and we generated the data that drove this discovery.

As a lab, our team is tailor-made to support these kinds of studies. We do everything from tissue extraction to laboratory work, bioinformatics and reporting, which allows the research teams we partner with to focus on analyzing the data and on engaging with patients.

OICR Genomics will also work with partners to use this technology to support other cutting-edge clinical trials. That means our collaborative efforts will ultimately have an impact on patients at all stages of their journey with cancer.

Blood test detects tumours early in families with cancer

Researchers from The Hospital for Sick Children (SickKids), the Ontario Institute for Cancer Research (OICR) and University Health Network (UHN) have demonstrated that by analyzing patients’ blood samples, they are able to detect cancer earlier in individuals with Li-Fraumeni syndrome (LFS), an inherited condition with an almost 100 percent lifetime risk of developing cancer.

The research, led by Drs. Trevor Pugh and Raymond Kim at Princess Margaret Cancer Centre, UHN and OICR and Dr. David Malkin at SickKids, has been published in Cancer Discovery. The study, which was funded primarily by The Terry Fox Research Institute, would not have been possible without the generosity of the patients who participated.

Li-Fraumeni syndrome is an inherited condition associated with a very high risk of developing cancer —often tumours affecting the breast, soft tissue, brain and other organs. It is caused by changes in the TP53 gene, which encodes a protein that helps to prevent tumour formation and is commonly termed the “guardian of the genome.”

Cancerous cells and healthy cells release pieces of DNA into the blood. By analyzing these DNA fragments, researchers are developing methods to detect whether a tumour has developed in the body. Testing blood samples for signs of cancer – often called liquid biopsies – is an attractive screening approach compared to imaging methods, which require specialized machines, and biopsies, which are more invasive.

The research team analyzed 170 blood samples from 82 individuals with Li-Fraumeni syndrome collected over several years, as well as 30 blood samples from individuals without Li-Fraumeni syndrome, providing a proof-of-principle framework that may support the detection of specific cancers earlier for individuals with Li-Fraumeni syndrome.

For Luana Locke and her family, early detection is invaluable and has prolonged her life many times already. Luana was diagnosed with breast cancer at age 25 and later discovered that her mother, children and many members of her extended family carried the same TP53 genetic change.

Luana, who has since had sarcoma, lung cancer, thyroid cancer and skin cancer, and her children have regular screenings, blood tests, MRIs of the entire body, and ultrasounds at Princess Margaret Cancer Centre and SickKids, to detect cancers early. After years of these scans Luana’s daughter, Juliet, was diagnosed with leukemia at age 14, a condition they have since learned may have been detected months earlier with this new blood sample analysis.

“Even though I have LFS, I never really felt cancer anxiety until after I was diagnosed,” says Juliet. “While my check-ups are reassuring, getting more precise diagnoses earlier is the next level in care.”

Dr. Malkin has been monitoring Luana’s children for almost 20 years, including her son who was one of the first people to follow a cancer surveillance protocol known as the “Toronto Protocol,” while Dr. Kim has been monitoring Luana for almost 10 years.

“This is a full circle moment for us. From being part of the first Toronto Protocol to what may now be the next step in early detection and diagnosis for families with LFS, our family has relied on the advancements made at SickKids and The Princess Margaret,” says Luana. “Regular scans and check-ups are routine when you have LFS, but the ability to predict when and where cancers develop rather than react when one has already developed would be life changing.”

The team will conduct a clinical trial to further test this approach and screen patients in the hope of finding their cancer earlier. These patients will include those with different types of high-risk cancer predisposition syndromes, including Li-Fraumeni syndrome, Lynch Syndrome, and Hereditary Breast and Ovarian Cancer; all of which are brought under a nation-wide research consortium that Drs. Pugh and Kim founded in 2017.

This work was supported by the Terry Fox Research Institute (www.tfri.ca) and Terry Fox Foundation, Canadian Institutes for Health Research, TD Ready Challenge, the McLaughlin Centre at the University of Toronto, Shar Foundation, FDC Foundation, Bhalwani Family Charitable Foundation, Karen Green and

George Fischer Genomics and Genetics Fund, Lindy Green Family Foundation, The Devine/Sucharda Charitable Foundation, SickKids Foundation, The Garron Family Cancer Centre, Children Tumour Foundation, The Princess Margaret Cancer Foundation and the Ontario Institute for Cancer Research. This work would not have been possible without the generosity of the patients who participated in this study.

Quotes

“Until now, the ways we did surveillance in children with cancer or in children with a genetic predisposition to cancer have been burdensome to families and the health care system – relying on multiple visits to the clinic, imaging tests and imprecise blood tests,” says Dr. David Malkin, Staff Oncologist, Senior Scientist and Director of the Cancer Genetics Program at SickKids and a Professor of Paediatrics and Medical Biophysics at U of T. “Now, we can use a simple blood test to identify when, and sometimes where, a cancer is occurring. That is precision. These promising findings can be extended to all hereditary cancer syndromes to help improve the accuracy of cancer detection, especially for common tumour types, utilizing several analysis types that leverage different biological measurements.”

“We used a combination of genomic, fragmentomic and epigenetic methods to analyze patients’ blood samples at a molecular level,” says Dr. Trevor Pugh, Senior Scientist at Princess Margaret Cancer Centre and Director of the Ontario Institute for Cancer Research (OICR) Genomics Program, where blood samples were analyzed. “The key to these long, multi-year studies is keeping up the momentum and building infrastructure to enable comparisons of multiple types of data over time. Here, we were able to detect multiple different types of DNA changes in blood that were a telltale sign that cancer was developing somewhere in the body months before cancer would show up in imaging.”

“Each of these methods were able to detect cancer-associated signals in the samples, but the integration of multiple analysesprovides a more holistic view of tumour DNA events. This more robust approach is paramount in early cancer detection where the stakes are high.” says Dr. Raymond Kim, Medical Director of Cancer Early Detection at the PM’s Bhalwani Familial Cancer Clinic and lead of the Ontario Hereditary Cancer Research Network at OICR. “To improve the accuracy of early-stage cancer diagnoses, such genetic tests can be used to complement other clinical screening methods, and they can be performed at a higher frequency.”

For more information, or to speak to the researchers involved, please contact:

Marina Jimenez
Communications Director, Princess Margaret Cancer Centre
Email: marina.jimenez@uhn.ca

Sarah Warr
Senior Communications Advisor, The Hospital for Sick Children (SickKids)
Email: sarah.warr@sickkids.ca

Student researcher collaborating with Indigenous community to improve cancer screening

OICR is hosting Jayson Pomfret as part of a unique summer internship program.

Jayson Pomfret understands that meaningful cancer research happens in the community as well as at the lab bench.

Pomfret is an undergraduate student in Queen’s University’s Bachelor of Health Sciences program who wants to pursue a career in medicine and science. He also believes strongly in population health research, and he is pursuing that interest during a unique summer internship.

Pomfret is part of the BioCanRx Indigenous Student Summer Internship Program co-funded by OICR and based at Sunnybrook Hospital. He is spending his summer contributing to a research project that aims to revamp communications materials for cancer screening programs in the Sioux Lookout First Nation in Northwestern Ontario.

OICR News recently asked Pomfret about his goals for the internship and for his future.

Why did you decide to study health sciences?

I’ve had interest in health sciences and medicine since I was younger, and that interest solidified when I had the opportunity to do a youth exchange program in the Czechia. I was hosted by two different physicians and their families while in the Czechia and I got an inside look at what it’s like to balance clinical practice with research, public health advocacy and other non-clinical medical-related interests. The ability to blend a professional career in medicine with a personal drive to better public health and undertake important research astounded and interested me quite a lot.

The project you’re working on during your internship is focused on population health for the Sioux Lookout First Nation. Why did that project interest you?

I’ve done significant academic course work in global population health as well as Indigenous population health. This project interested me because it applies that population health lens to improve cancer screening in a community where it is very much needed. And, as an Indigenous student myself, I find it imperative to use my time and resources to conduct research that can directly benefit Indigenous populations.

Can you tell us more about the project?

Indigenous populations, and specifically the Indigenous population in Northwestern Ontario, are dying of cancers like colorectal cancer at a significantly higher rate than people in Southern Ontario. One of the best ways to remedy this inequity is through effective cancer screening. But the current letters and forms sent out to the Sioux Lookout community and other communities across Ontario about the colorectal cancer screening program are quite technical and are certainly not representative of Indigenous health needs or longstanding cultural health knowledge.

My research is focused on integrating cultural safety within the ways the colorectal screening program and other screening programs under Ontario Health are communicated to the communities under the healthcare oversight of the Sioux Lookout First Nations Health Authority. I think it’s necessary to overhaul those communication materials before we can look at other interventions, so that there can be a higher level of screening to address cancer inequities in a prophylactic manner.

Can you tell us more about ‘cultural safety’ and what it means in this project?

It boils down to a couple of things in this context. One aspect is data sovereignty, and the ability for Indigenous populations to control their own data, have access to that data, and own that data. I had the opportunity to travel to Thunder Bay and speak with members of the community regarding data sovereignty. What I heard was that the community has very little trust that their data will be protected, respected and represented accurately. So that trust needs to be rebuilt.

The other aspect is making sure communications strategies around cancer screening recognize and respect Indigenous knowledge and the sacred traditions of healthcare in those communities, which isn’t the case currently.

What are your goals for your internship?

Though it’s only a three-month internship, I’m hoping to make significant contributions to the project by building relationships with the community in Sioux Lookout and listening to their needs. I think that’s the most important thing, to listen to people and hear their priorities for cancer screening, instead of just trying to overhaul the screening program from the perspective of somebody who lives in Southern Ontario.

Personally, I hope to gain a whole new perspective on research and how it can lead to actionable policy outcomes. I think that will open a wide variety of different paths I can take with my career alongside medicine.

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