September 16, 2020

Scientists discover mechanism of bone loss caused by acute lymphocytic leukemia, identify targeted therapy for children

Two young girls play in a pile of autumn leaves.

OICR-supported research team discovers new pathway through which leukemia cells damage bone and a treatment that may protect children with leukemia from these effects

Due to remarkable progress in the treatment of pediatric leukemias with multi-drug chemotherapy, upwards of 85 per cent of children with the disease survive. One consequence of this success, is that more than a third of these patients suffer from in-bone fractures and pain during leukemia and for years following their treatment. In a recent study, Ontario researchers at the Hospital for Sick Children (SickKids) have discovered a process by which leukemia cells damage bone and discover that a targeted therapy may be able to prevent this damage.

In their study, published in Science Translational Medicine, the research group discovered that the bone degradation in leukemia patients is triggered by a protein called RANKL on the surface of the leukemic cells interacting with receptors called RANK on the surface of bone-degrading cells. The group showed that a drug, which is similar to one that is currently in clinical trials for other cancers, could specifically block this RANKL-RANK interaction and prevent further bone damage.

“A pan-Canadian study demonstrated that 15 per cent of children display bone fractures at the time they are diagnosed with acute lymphocytic leukemia, or ALL,” says lead author Dr. Jayne Danska, Senior Scientist in the Genetics & Genome Biology program at SickKids and Associate Chief, Faculty Development and Diversity at the SickKids Research Institute. “In addition, standard ALL chemotherapy protocols include corticosteroids which further damage the bone. Survivors of childhood ALL experience fractures and pain, and some cases are so severe that they require a hip replacement in their teenage years. We have discovered one mechanism that contributes to ALL-associated bone damage and a potential way to prevent it.”

To make these discoveries, first author of the study, Dr. Sujeetha Rajakumar, a postdoctoral fellow at SickKids, transplanted ALL cells from patient donors into experimental mouse models to examine the effect of leukemia cells on bone and how to disrupt the RANKL-RANK interaction. This so-called xenotransplantation method was pioneered by Dr. John Dick at the University Health Network’s Princess Margaret Cancer Centre.

Using these animal models, Danska’s group showed that treatment of the ALL-transplanted mice with a protein therapeutic that blocks the RANKL-RANK interaction prevented bone damage despite high number of leukemia cells in the bone compartments.

“There are clinical trials underway to test whether RANKL-RANK antagonists can prevent bone degradation in adults with metastatic prostate and breast cancers,” says Danska, who is also a Professor in the University of Toronto’s Faculty of Medicine. “The data we report in the human ALL transplant model is encouraging because the availability of clinical data with this class of drug can accelerate application of our discoveries to clinical trials in youth with ALL.”

“Children with leukemia sustain unbelievably rigorous and lengthy chemotherapy treatments,” says Danska. “We’re eager to bring our discoveries into clinical trials that may help minimize these painful and life-altering late effects of this disease.”

Danska and study collaborators Drs. Cynthia Guidos and Johann Hitzler of SickKids, and Drs. Mark Minden and John Dick of the Princess Margaret Cancer Centre are members of OICR’s Acute Leukemia Translational Research Initiative (TRI), which partially funded the study.

Read more about the Acute Leukemia TRI or more about OICR’s latest leukemia research news.

September 3, 2020

Analyzing SARS-CoV-2: A cancer researcher trainee’s perspective

OICR-based PhD Candidate awarded University of Toronto COVID-19 Student Engagement Award

This scanning electron microscope image shows SARS-CoV-2 (round blue objects) emerging from the surface of cells cultured in the lab. SARS-CoV-2, also known as 2019-nCoV, is the virus that causes COVID-19. The virus shown was isolated from a patient in the U.S. Credit: NIAID-RML
This scanning electron microscope image shows SARS-CoV-2 (round blue objects) emerging from the surface of cells cultured in the lab. SARS-CoV-2, also known as 2019-nCoV, is the virus that causes COVID-19. The virus shown was isolated from a patient in the U.S. Credit: NIAID-RML

When the COVID-19 pandemic shut down labs across Canada, cancer research trainees looked for ways to help respond to the pandemic. PhD candidates Tom Ouellette and Jim Shaw saw an opportunity to combine their skills and contribute to the cause.

Ouellette and Shaw were recently awarded a University of Toronto COVID-19 Student Engagement Award for their project titled Network and evolutionary analysis of SARS-CoV-2: A vaccine perspective. Together, they will develop new machine learning tools to analyze the SARS-CoV-2 genome and how it evolves. 

Tom Ouellette, PhD Candidate in Dr. Philip Awadalla’s lab at OICR.

“We’re two like-minded individuals with complementary skillsets who enjoy coding, math and solving problems, which – fortunately – can be done remotely,” says Ouellette, who is a PhD Candidate in Dr. Philip Awadalla’s lab at OICR. “We saw the opportunity to help with COVID-19 research and we’re happy to apply our skills to help advance research towards new solutions for this pressing problem.”

Ouellette specializes in evolution and population genetics and Shaw specializes in network analysis and algorithm development. Through this award, they will investigate how SARS-CoV-2 is evolving by looking into specific regions of the virus’ genetic code from samples around the world, using mathematical modelling, machine learning, and evolutionary simulations. They are specifically interested in how these changes in the genetic code may alter the virulence, or severity, of the virus.

Jim Shaw, PhD Candidate in mathematics at the University of Toronto.

“Just like cancer, different pressures or stresses can make viruses evolve,” says Shaw, who is a PhD Candidate in mathematics at the University of Toronto. “Understanding these changes can have an impact on how we build vaccines. Furthermore, better understanding of the virus’ evolution may shed light on viral reinfection, which is an important issue as we move into the later stages of the pandemic.”

Ouellette and Shaw plan to publicly release the code that they develop through this initiative for other researchers to build upon.

“SARS-CoV-2 has a much simpler genome than a cancer genome, so it can serve as a simplified model to test out new analytical techniques,” says Ouellette. “Ultimately, I hope to bring the tools and technology we create back into my research on cancer so we can better understand how cancer evolves and becomes resistant to treatment.”

Read more on how OICR researchers are helping understand and overcome COVID-19

August 28, 2020

Tumour traces in blood could predict which cancer patients will benefit from immunotherapy

OICR-supported researchers and collaborators discover indicators in the blood that may predict which patients will respond to the immunotherapy drug, pembrolizumab

Dr. Scott Bratman, Cindy Yang, Dr. Lillian Siu, Dr. Trevor Pugh

Adapted from UHN’s Media Release.

Immunotherapy can shrink tumours and prolong survival for certain cancer patients, but clinicians don’t yet know which patients will benefit from these treatments. OICR-supported researchers and collaborators at the Princess Margaret Cancer Centre have made a discovery that could help identify those patients who may benefit and match them with potentially life-saving therapies.

In their study, recently published in Nature Cancer, the research group found that the changing levels of tumour fragments, or circulating tumour DNA (ctDNA), in a patient’s blood can be used to predict whether they will respond to the immunotherapy drug pembrolizumab.

The study lays the foundation for researchers to develop an easy, non-invasive and quick blood test to determine who will benefit from the drug and how well their disease is responding to treatment.

“While we have known for some time that cancer disease burden can be monitored by measuring tumour DNA in the blood, we are excited to report that the same concept can be applied to track the progress of patients being treated with pembrolizumab,” says co-first author Cindy Yang, PhD Candidate in Dr. Trevor Pugh’s lab at the Princess Margaret Cancer Centre and OICR. “This will hopefully provide a new tool to more accurately detect response and progression in patients undergoing immune checkpoint inhibitor therapy. By detecting progression early, patients may have the opportunity to undergo subsequent lines of treatment in a timely fashion.”

The benefits of blood tests

Conventionally, imaging scans – such as computerized tomography (CT) scans – and other methods are used to monitor a patient’s cancer. This study suggests a simple and quicker blood test as an alternative to these scans.

“Although important, computerized tomography (CT) and other scans alone will not tell us what we need to know quickly or accurately enough,” says senior author Dr. Lillian Siu, Senior Scientist and medical oncologist at the Princess Margaret Cancer Centre.

Dr. Scott Bratman, radiation oncologist and Senior Scientist at the Princess Margaret Cancer Centre and co-first author of the study, points out that it may take many months to detect whether a tumour is shrinking with various imaging scans. 

“New next-generation sequencing technologies can detect and measure these tiny bits of cellular debris floating in the blood stream accurately and sensitively, allowing us to pinpoint quite quickly whether the cancer is active.”

This study represents one of the many emerging applications of using ctDNA to guide treatment decisions. It is one of the first to show that measuring ctDNA could be useful as a predictor of who responds well to immunotherapy across a broad spectrum of cancer types. 

The prospective study analyzed the change in ctDNA from 74 patients, with different types of advanced cancers, being treated with pembrolizumab. Of the 74 patients, 33 had a decrease in ctDNA levels from their original baseline levels to week six to seven after treatment with the drug. These patients had better treatment responses and longer survival. Even more striking was that all 12 patients who had clearance of the ctDNA to undetectable levels during treatment were still alive at a median follow-up of 25 months.   

Conversely, a rise in ctDNA levels was linked to a rapid disease progression in most patients, and poorer survival.   

“Few studies have used a clinical biomarker across different types of cancers,” says Siu, who also co-leads OICR’s OCTANE trial. “The observation that ctDNA clearance during treatment and its link to long-term survival is novel and provocative, suggesting that this biological marker can have broad clinical impact.” 

Innovation and translation

This study is part of a larger flagship clinical trial, INSPIRE, which has enrolled more than 100 patients with head and neck, breast, ovarian, melanoma and other advanced solid tumours. INSPIRE brings together researchers from many disciplines to investigate the specific genomic and immune biomarkers in patients that may predict how patients will respond to pembrolizumab.

INSPIRE is made possible by collaborations across institutes and industries with expertise from those applying genomics to research and those applying genomics in the clinic.

“INSPIRE is an incredibly collaborative initiative that is a blend of big genomics – looking at large trends across many individuals – and highly-personalized genomics – looking at mutations within each patient sample,” says Pugh, co-senior author, Senior Scientist at Princess Margaret and Senior Investigator and Director of Genomics at OICR. “This is a modern approach to the translation of clinical genomics.”

“As a PhD student, this project gave me the unique opportunity to work in a highly collaborative intersection with industry, clinical, and academic partners,” says Yang. “It is very exciting to see translational research in action.”

Read the UHN Media Release.

July 29, 2020

Q&A with new OICR investigator Dr. Courtney Jones on benefitting patients through research

OICR welcomes Dr. Courtney Jones to Ontario’s cancer research community

Courtney Jones

Starting up an independent research lab in the midst of a pandemic is difficult but Dr. Courtney Jones is up for the challenge. Jones moved to Canada prior to the lockdown and has been gearing up for new experiments since. Now, as an OICR Investigator, she has safely started working in her lab at the Princess Margaret Cancer Centre to find new solutions for the leading cause of leukemia deaths in Canada – acute myeloid leukemia (AML).

Continue reading – Q&A with new OICR investigator Dr. Courtney Jones on benefitting patients through research

July 8, 2020

Protecting cancer patients from COVID-19: world-first clinical trial tests a novel immune-boosting strategy

Dr. Rebecca Auer with colleague. Credit: The Ottawa Hospital

In the race to find new ways to prevent and treat COVID-19, OICR-supported researchers have launched an innovative clinical trial focussed on strengthening the immune system for one of the most vulnerable populations – cancer patients.

The trial involves IMM-101, a preparation of safe, heat-killed bacteria that broadly stimulates the innate, or “first-response,” arm of the immune system. The researchers hope that boosting cancer patients’ immune systems with IMM-101 will protect them from developing severe COVID-19 and other dangerous lung infections.

Researchers from The Ottawa Hospital came up with the idea for the trial and worked with the Canadian Cancer Trials Group (CCTG) at Queen’s University to design and run it in centres across the country. Funding and in-kind support, valued at $2.8 million, is being provided by the Canadian Cancer Society, BioCanRx, the Ontario Institute for Cancer Research, The Ottawa Hospital Foundation, The Ottawa Hospital Academic Medical Organization, ATGen Canada/NKMax, and Immodulon Therapeutics, the manufacturer of IMM-101.

“An effective vaccine that provides specific protection against COVID-19 could take another year or more to develop, test, and implement,” says Dr. Rebecca Auer, study lead, surgical oncologist and Director of Cancer Research at The Ottawa Hospital and associate professor at the University of Ottawa. “In the meantime, there is an urgent need to protect people with cancer from severe COVID-19 infection, and we think this immune stimulator, IMM-101, may be able to do this.”

“This trial could support an important change to the standard of care for cancer patients by administration of IMM-101 prior to starting cancer treatment,” says Dr. John Bell, Senior Scientist at the Ottawa Hospital Research Institute, Scientific Director of BioCanRx and co-lead of OICR’s Immuno-oncology Translational Research Intitiative. “Accelerating to the clinic, biotherapeutics that can enhance the quality of life of those living with cancer.”

The trial, called CCTG IC.8, has been approved by Health Canada and is expected to open at cancer centres across Canada this summer. People who are interested in participating should speak with their cancer specialist.

“OICR is excited to be collaborating on such a landmark clinical trial supporting cancer patients in this unprecedented time,” says Dr. Laszlo Radvanyi, President and Scientific Director, OICR. “IMM-101 may be an effective approach to protect our vulnerable patients not only against COVID-19, but also to boost their immune system to fight cancer.”

Read the full release.

June 25, 2020

CanPath Awarded $2.1 million CIHR Grant for SUPPORT-Canada COVID-19 Initiative

The SUPPORT-Canada initiative will capture data and biospecimens in order to identify factors contributing to COVID-19 susceptibility, severity and outcomes.

Dr. Philip Awadalla

CanPath (the Canadian Partnership for Tomorrow’s Health), co-led by OICR Investigator Dr. Philip Awadalla, has been awarded a $2.1 million grant from the Canadian Institutes of Health Research (CIHR) through their COVID-19 Rapid Research Funding competition. The initiative, titled SUrveying Prospective Population cOhorts for COVID-19 pRevalence and ouTcomes in Canada (SUPPORT-Canada),aims to capture data and biospecimens to enable population-level surveillance. SUPPORT-Canada will enable researchers and clinicians to find factors contributing to COVID-19 susceptibility, severity and outcomes, thus identifying factors predisposing individuals or communities across Canada to a high risk of infection.

“The integration of clinical programs with our broader existing population cohort infrastructure creates the opportunity to rapidly assess patterns across Canada, while discovering and tracking critical biological and environmental determinants of disease susceptibility and severity for COVID-19,” says Awadalla, who is the lead Principal Investigator for the SUPPORT-Canada Initiative and National Scientific Director of CanPath.

Continue reading – CanPath Awarded $2.1 million CIHR Grant for SUPPORT-Canada COVID-19 Initiative

June 9, 2020

FACIT recognized with 2020 Venture Capital Regional Impact Award by the Canadian Venture Capital & Private Equity Association (CVCA)

Award acknowledges FACIT’s commercialization impact in growing Ontario’s life sciences industry

FACIT, a commercialization venture firm, has been nationally recognized with CVCA’s 2020 Venture Capital Regional Impact Award for Ontario. The CVCA helps to set the foundation for greater collaboration, innovation, growth and market intelligence for Canadian private capital professionals. The Venture Capital Regional Impact Award celebrates firms whose investments have positioned portfolio companies to make a meaningful mark within both their community as well as the broader niche sector. The award competition considers the most impactful private equity organizations across all sectors including IT, AgTech, Healthcare, and CleanTech.

FACIT’s award was specifically related to the 2019 historic US$1B partnership between its portfolio companies, Propellon Therapeutics (“Propellon”) and Triphase Accelerator (“Triphase”), and US pharma giant Celgene (acquired by Bristol-Myers Squibb Company). The partnership represents one of the largest oncology licensing transactions for a preclinical asset in Canadian history, and the largest biotech asset transaction worldwide for academia. Moreover, this deal helped to solidify a “made in Ontario” development pathway for commercialization of oncology innovations, as the asset at the heart of the transaction originated from FACIT’s strategic partner, the Ontario Institute for Cancer Research (OICR). FACIT’s strategic seed investment of $3M was critical in putting Ontario intellectual property (IP) in a position of strength to negotiate a transaction with maximum regional impact. The collaboration with Triphase anchors R&D jobs, clinical trials and industrial development in Ontario, benefiting both the economy and patients. 

Through financial support from Ontario’s Ministry of Colleges and Universities, FACIT has a mandate to translate Ontario’s most promising cancer innovations and maximize the value of the province’s investment in research and healthcare. With a portfolio that has attracted over $850 million in investment to Ontario, FACIT is actively building companies with entrepreneurs to accelerate healthcare innovation and retain IP value, jobs and industrial development in Canada. Its success in locally commercializing medical technology, health IT, imaging, and therapeutics is a direct result of the integration of outstanding science, Ontario First seed capital, and industry experience into a novel commercialization venture model. Not only have FACIT-supported ventures attracted remarkable life science financings, but every dollar invested by FACIT has attracted $20 dollars of private equity to the province.

“We are proud of the team’s work to help demonstrate the value of seed-stage investing in the commercialization of Propellon and Triphase, and we thank CVCA for this honour and recognition by our industry peers,” said Dr. David O’Neill, President of FACIT. “The rapid growth of our portfolio demonstrates the power of biotechnology to capitalize on Ontario’s world-class cancer science, compete in the innovation economy and make a difference in the fight against cancer.”

“This is a great achievement and recognition that FACIT is successfully driving significant benefits to the Ontario innovation economy, building on the research strength of OICR,” said Dr. Laszlo Radvanyi, President and Scientific Director of OICR.

“Congratulations to FACIT on receiving the CVCA award for their leadership in Ontario’s commercialization sector,” said the Honourable Ross Romano, Minister of Colleges and Universities. “FACIT has made smart and strategic investments in Ontario’s rapidly developing biotech sector. The firm is an important partner in ensuring that the province’s intellectual property is captured, both for the local economy and patients living with cancer.”

Read more on facit.ca.

May 21, 2020

Q&A with Monique Albert: Ontario’s international leader in biobanking

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.

Read more about ISBER’s 2020 Election Results or more on Monique Albert’s active role within ISBER on OICR News.  

May 6, 2020

New treatment for recurrent pediatric brain cancer enters clinical testing

Dr. Michael Taylor
Dr. Michael Taylor

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.

Read SickKids news release.

April 16, 2020

University students step up to flatten the COVID curve

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.

Yifei Zhang, Vice President of Flatten.

“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.

March 24, 2020

The donations behind the discoveries: The Ontarians who made the Pan-Cancer Project possible

A technician at an Ontario Tumour Bank site at Kingston General Hospital works with frozen specimens.

The Pan-Cancer project made international headlines this month, but not without the contributions of thousands of individuals and the teams that preserve their specimens

In an unprecedented, decade-long study of whole cancer genomes, OICR researchers and collaborators have improved our fundamental understanding of the disease, indicating new directions for developing diagnostics and treatments. The Project was powered by 2,800 people with cancer who donated their biologic specimens to research. These contributions were facilitated and protected by groups such as the Ontario Tumour Bank (OTB).

From the operating room to the freezer

Many advances in cancer research, like those made by the Pan-Cancer Project, rely on hundreds – and sometimes thousands – of biospecimens. A patient’s donated blood, tumour and surrounding tissue may hold clues to future innovations in cancer diagnostics and therapies. But without biobanks – the repositories that collect and care for biological samples – the clues within these donations may never be discovered.

“Good science is built on good data and good omics data can only be drawn from well-preserved tissues,” says Monique Albert. “The advancements made by the Pan-Cancer Project would not have been possible without the diligent work of biobanking teams.”

Albert is the Director of OTB – a provincial bioresource operating in partnership with four state-of-the-art hospitals and cancer centres across Ontario. OTB plays a quiet but crucial role between the patient and the researcher, providing the fundamental biologic resources that research is built on.

Lowering the temperature and raising the bar

Day-to-day, biobanking teams – like OTB – work to implement the highest standards of preservation. From the operating room to the freezer and back to the lab, these teams tirelessly strive to maintain the quality of patient samples to inform cancer discoveries. OTB has held and raised leading biobanking standards for over 15 years.

“When The Cancer Genome Atlas started, biobanks around the world promised thousands of samples, but only a fraction of these samples were adequate for research,” says Albert, referring to Libraries of Flesh: The Sorry State of Human Tissue Storage. “This served as a wake-up call for the sector to unite, share best practices and set higher standards together.”

At the launch of The Cancer Genome Atlas (TCGA) in the early 2000s, OTB was up to – and in many ways exceeded – existing biobanking standards. This was thanks to the foresight of Dr. Brent Zanke and Sugy Kodeeswaran, who recognized the importance of stringent biobanking practices nearly a decade before biobanking became popularized.

As the only Canadian repository that was able to contribute to TCGA, OTB allowed hundreds of people from Ontario to contribute to this international initiative and to subsequent studies like the Pan-Cancer Project.

Since its inception, OTB has collected more than 185,000 samples donated by more than 21,000 individuals from across Ontario, enabling these donations to have a greater impact today and for years to come.

“Each sample represents a trace of an individual’s life, and we’re honoured to care for these valuable donations to science,” says Albert. “When they’re preserved properly, they become a lasting resource with infinite value. We’re proud that the donations from Ontario patients are paving the way for better and more targeted cancer treatment.”

OTB plays a critical role in leading the development of Canadian biobanking standards through the Canadian Tissue Repository Network (CTRNet), and biobanking standards around the world through the International Society for Biological and Environmental Repositories (ISBER).

Read more about OTB’s research resources and how OTB is collaborating to improve biobanking around the world by visiting their website at ontariotumourbank.ca.

March 2, 2020

Study reveals roots of leukemia that current chemotherapies can’t reach

John Dick

Researchers find the roots of leukemia relapse are present at diagnosis, uncovering clues to new treatment approaches

Despite significant advances in the treatment of acute lymphoblastic leukemia (ALL), the disease often returns aggressively in many patients after treatment. It is thought that current chemotherapies eliminate most leukemia cells, but groups of resistant cells may survive therapy, progress and eventually cause relapse. Dr. John Dick and collaborators have found these cells.

In a recent study published in Cancer Discovery, Dick and collaborators were able to identify and isolate groups of genetically distinct cells that drive ALL relapse.

The cells, termed diagnosis relapse initiating (dRI) clones were found to have genetic characteristics that differ from the other leukemia cells that are eliminated by treatment.

The study, along with a complementary study published in Blood Cancer Discovery, unraveled the genetic, epigenetic, metabolic and pro-survival molecular pathways driving treatment resistance. Together, these papers provide an integrated genomic and functional approach to describing the underlying genetics and mechanisms of relapse for ALL.

Interestingly, the research group discovered that dRI clones are present at diagnosis, opening opportunities to improve treatment up-front, devise drugs that target these resistant cells and prevent relapse from ever occurring.

Dr. Stephanie Dobson

“Our study has shown that genetic clones that contribute to disease recurrence already possess characteristics such as therapeutic tolerance that distinguish them from other clones at diagnosis,” says Dr. Stephanie Dobson, first author of the study who performed this research as a member of John Dick’s Lab. “Being able to isolate these clones at diagnosis, sometimes years prior to disease recurrence, has enabled us to begin to profile the properties allowing these particular cells to survive and act as reservoirs for relapse. This knowledge can be used to enhance our therapeutic approaches for targeting relapse and relapse-fated cells.”

“Xenografting added considerable new insight into the evolutionary fates and patterns of subclones obtained from diagnosis samples,” says John Dick, who is the co-senior author of the study, Senior Scientist at the Princess Margaret Cancer Centre and leader of OICR’s Acute Leukemia Translational Research Initiative. “We were able to gather extensive information about the genetics of the subclones from our models, which helped us describe the trajectories of each subclone and the order in which they acquired mutations.”

Ordering these mutations relied on the advanced machine learning algorithms designed by Dr. Quaid Morris and Jeff Wintersinger at the University of Toronto.

Research efforts are underway to build on these discoveries and determine how to block dRI clones.

The study was led by researchers at St. Jude Children’s Research Hospital, the Princess Margaret Cancer Centre and the University of Toronto and supported in part by OICR’s Acute Leukemia Translational Research Initiative.

This post has been adapted from the St. Jude Children’s Research Hospital news release.

Next Page »