February 26, 2021

Bringing AI-enabled cancer support to life

Text-based online support groups augmented with a new tool for detecting distress

Therapist-led online support groups can provide a safe space for people affected by cancer to discuss fear, normalize stress, build resilience and enhance coping. Cancer Chat Canada offers real time text-based support groups, but therapists who lead these groups often feel challenged to address the needs of each participant in the absence of visual cues. Recent Ontario-made advances in artificial intelligence (AI) may offer potential solutions.

In a paper recently published in JMIR Research Protocols, an Ontario-based research group outlines their new AI-enabled virtual therapy cofacilitator tool for online cancer support groups. The tool uses a machine learning algorithm based on interpreting patterns of speech and language to track support group participants’ progress in real-time, while providing feedback to the leading therapist.

The research initiative was supported by OICR through the OICR-Cancer Care Ontario (Ontario Health) Health Services Research Network, and led by Drs. Yvonne Leung and Mary Jane Esplen, experts in the psychological impact of cancer.

Workflow of how the chatbot works.

“Online support groups are accessible and effective at reducing cancer-related emotional distress, but it can be challenging to monitor individual participant distress and engagement while responding to multiple participants’ messages simultaneously,” says project lead Esplen, Professor and Vice-Chair, Equity and Mentorship in the Department of Psychiatry, University of Toronto and former Lead of the de Souza Institute. “With multiple participants typing at the same time, nuances of text messages and red flags for distress can sometimes be missed. Our tool serves as an AI-enabled cofacilitator that can enhance the therapist’s ability to address these concerns.”

With a tool that can detect and flag issues, therapists could prioritize concerns more effectively, provide more individualized support in real time, and direct treatment accordingly in a timely manner.

In 2020, the research group completed the first phase of their study, during which they developed the AI-enabled cofacilitator tool. Now, in the second phase, they are evaluating the tool’s effectiveness by scoring its ability to accurately output psychometric measures, such as fear, sadness and hopelessness.

“The goal is to visualize emotions and sentiments throughout therapy to make online group therapy more effective,” says first author Leung, who is an Assistant Professor at the University of Toronto. “We believe these tools and technologies can be used to strengthen person-centred care by attending to individual needs and expanding access to high-quality virtual health care. We’re delighted to be in the process of validating such a cutting-edge tool.”

Should effectiveness be demonstrated in their clinical studies, the group plans to integrate their AI-enabled cofacilitator into Cancer Chat Canada’s online psychosocial oncology services, and potentially adapt the cofacilitator algorithm for other cancer-related support services.

“We’re proud of the progress made so far,” says Esplen. “Our team was strategically built to incorporate different areas of expertise and different perspectives. We’ve tested each step along the way, and we look forward to building more tools to enhance patient therapy and care.”

Read more about the OICR-CCO Health Services Research Network on OICR News.

February 17, 2021

OICR’s Dr. John Bartlett named one of the top-cited authors in the Journal of Clinical Oncology

Dr. John Bartlett

The Journal of Clinical Oncology (JCO), one of the most prestigious journals in cancer research, recently added Dr. John Bartlett to its list of most-cited authors following an analysis by the analytics firm Clarivate. A clinical practice guideline update by Bartlett and his coauthors was the third most-cited article JCO published in 2018. The guideline, on HER2 testing in breast cancer, has been cited an outstanding 276 times. Bartlett is Director of OICR’s Diagnostic Development Program, which is working to develop new tools to guide precision medicine for cancer.

February 3, 2021

Standards redefined: What lab accreditation means to OICR Genomics

OICR Genomics believes high-quality cancer research starts with high-quality data. Since inception, their labs have been committed to quality, and now accreditation is within reach

Standards are all around us – making our lives safer and easier in many ways. In both research and medicine, laboratory standards help evaluate a lab’s quality, reliability and efficiency. Research lab standards help scientists generate reliable data leading to reproducible discoveries, but in medicine, lab standards help clinicians make more accurate diagnoses and treatment decisions. These different applications call for different standards and sometimes different schools of thought.

Since inception, OICR Genomics has been building a bridge between research and medicine, developing new standards for innovative genomics technologies while refining lab procedures so they can serve as the trusted genomics services provider for Ontario’s cancer community. Today, OICR Genomics is proud to provide high-quality services for cancer researchers, clinicians, and the patients they serve.

The journey to accreditation

Achieving and maintaining accreditation is an exceptionally rigorous process that requires steadfast diligence and meticulous lab management over a sustained period of time. Since 2018, OICR Genomics has been developing and improving processes and procedures to achieve accreditation by the Institute for Quality Management in Healthcare (IQMH) and the College of American Pathologists (CAP), two well-recognized leaders in lab accreditation.

There are three key elements that make accreditation possible:

Dedicated people. Every member of OICR Genomics is important to the accreditation process. Accreditation requirements include effective documentation and training protocols, a strong track record of good lab practices, continuous sharing and monitoring of technical results, appropriate validation and uncertainty correction methods, an extensive array of standard operating procedures, and more. Successful accreditation requires the collective effort of all lab staff – from students to senior researchers.

“I’m proud of our team’s commitment to the community,” says Dr. Carolyn Ptak, Program Manager and Quality Assurance Lead of OICR Genomics. “We have a great group that is flexible, innovative and committed to quality.

Balanced priorities. Given the complex and rapidly evolving field of cancer genomics, many laboratories face challenges associated with compliance. New tools and innovations call for new standards. OICR Genomics continuously strives to balance innovation, performance, efficiency and safety under the leadership of Dr. Trevor Pugh.

“As research continues to evolve, OICR Genomics will continue to as well,” says Dr. Trevor Pugh, Senior Investigator and Director of the Joint Genomics Program at OICR and the Princess Margaret Cancer Centre. “We’re excited by the current advancements in genomics and we look forward to continuous improvement in the years to come.”

Stable support. Over the last fifteen years, OICR has mobilized the community to transform cancer care through collaborative networks, transformative initiatives and more. Many collaborators have recognized the value of working with OICR Genomics and it is with their consistent support that the foundations leading to accreditation were laid.

“We are thankful for all the talented scientists who have worked with us throughout the years on innumerable genomic sequencing projects,” says Dr. Paul Krzyzanowski, Director of the Genome Research Platform,  “Our  newly accredited services will be available to clinical, academic, and industrial research clients and we’re excited to be able to support a whole new scale and scope of projects.

For the community

Genomics has become a central discipline of cancer research. It has unlocked new opportunities to predict cancer earlier and match patients with the most effective medicines for their disease. In parallel, advances in research methods and sequencing technologies have expanded the affordability and accessibility of genetic sequencing. Reading human DNA and RNA is no longer a multi-year, multi-million-dollar initiative, it can be done in hours or days at a fraction of that cost. These opportunities, however, can only be realized through the translation of research and innovation. For OICR Genomics, translation is at the centre of their mission – and rigorous lab standards help accelerate translation.

Within the cancer community, OICR Genomics’ lab standards can mean different things to different people:

  • For the researcher, high lab standards and accredited lab services help you generate high-quality, reliable data in an efficient way. This means you can have more trust in your results and more reproducible discoveries.
  • For the patient, high lab standards can help ensure that the community is effectively gaining knowledge from your donated biological samples. Accreditation of your local genomics research lab can also help your care teams apply the most recent discoveries to your treatment planning.
  • For the province, these internationally recognized standards will help research teams use resources efficiently and effectively, maximizing the impact of finite resources, while attracting high-profile genomic studies to Ontario.

“Accreditation allows us to explore transformative new approaches to achieve health benefits,” says Dr. Laszlo Radvanyi, President and Scientific Director of OICR. “Ultimately, accredited lab protocols help our lab infrastructure serve as bridge between research and improved health.”

For more information on OICR Genomics’ services please visit the genomics services page or contact OICR Genomics.

January 27, 2021

OICR-led research well represented in Nature Communications’ editor’s selections

The high-impact, open-source journal Nature Communications has published an editor’s selection of interesting, recently published studies that “significantly move forward the rapid evolving field of cancer research”. OICR is prominently featured with eight of the 41 studies selected having an OICR senior researcher as an author. Many of the highlighted findings stem from the Pan-Cancer Analysis of Whole Genomes project, an unprecedented global collaboration led in part by OICR that generated the most comprehensive map of cancer genomes charted to date.

December 17, 2020

nanoNOMe: New dual-purpose tool added to the Swiss Army knife of DNA sequencing

Dr. Jared Simpson and collaborators develop new nanopore-based methods to investigate two understudied aspects of disease biology

Studying DNA modifications may offer new insights into cancer – and the tools to read these changes are now in our hands.

In a recent publication in Nature Methods, OICR Investigator Dr. Jared Simpson and collaborators at Johns Hopkins University describe a new method to investigate two key aspects of disease biology, methylation and chromatin accessibility, simultaneously. These aspects can help describe how genes are organized and switched on and off in a cell, which may enable future progress in cancer research and discovery.

The group’s new method, coined nanoNOMe-seq, is built for nanopore sequencing – a fast, portable way to read long molecules of DNA. nanoNOMe serves as an additional tool that extends the utility of nanopore sequencing technologies.

“Our collaborators developed the lab protocols and we developed the analysis software to determine where DNA modifications occurred,” says Simpson. “Now, with this method, other researchers can investigate how DNA is modified within a cell to give an extra layer of information that the community can decode into new insights and discoveries.”

Dr. Michael Molnar, Scientific Associate in the Simpson Lab at OICR, led the development of the analysis software behind nanoNOMe.

“At times, it seemed like it might not be possible to develop a statistical model that could make sense of all the data,” says Molnar. “But we were able to persist and develop the nanoNOMe software, which showed a high degree of accuracy. We hope this method will enable others to discover long-range patterns and make new connections in sequencing data.”

nanoNOMe was first released as a preprint, which has already been cited in other scholarly articles including a tool for methylation pattern visualization, an analysis of human chromosome 8, and a published review on long-read sequencing among other publications. Simpson and Molnar’s collaborators plan to further investigate methylation and chromatin accessibility in human cancer cells with nanoNOMe.

“If you’re interested in understanding how methylation relates to open chromatin, then you can use this protocol,” says Simpson. “This is opening a new space for the community to explore interactions between chromatin and DNA methylation.”

December 2, 2020

Study uncovers new approach to mobilize the immune system against hard-to-treat breast cancers

Dr. Sam Workenhe. (University of Guelph)

Researchers at the University of Guelph and McMaster University create combination immunotherapy approach to treat breast tumours and other cancers

Over the last few decades, scientists have made significant progress in harnessing the immune system to treat cancers. Despite these advances, many types of cancer can still evade the immune system and current immunotherapies. Dr. Sam Workenhe is developing better treatment options for patients with these hard-to-treat diseases.

In his recent study, published in Nature Communications Biology, Workenhe and collaborators at the University of Guelph and McMaster University discovered a new combination immunotherapy approach for breast tumours and other cancers. Their approach leverages cancer-killing viruses, called oncolytic viruses, and chemotherapy to trigger tumour inflammation, stimulating the body’s immune system to control tumour growth. Their combination leveraged the oncolytic virus, oHSV-1, and the chemotherapy agent, Mitomycin-C.

The research team demonstrated the effectiveness of this treatment approach in mouse models of breast cancer. They found that that mice treated with this combination therapy lived approximately two months longer than untreated ones – a significant difference relative to the short lifespan of these mouse models.

“Simply put, we wake up the immune system,” says Workenhe, Assistant Professor at the University of Guelph’s Ontario Veterinary College and an OICR Joseph and Wolf Lebovic Fellowship Program awardee. “Our study proves that aggressive tumours without immune cells can be made to render an immune response. Understanding how to design treatments that can potentially activate the immune system against cancer can revolutionize the current standards of care.”

Additionally, the study delineated the anticancer mechanisms of their approach, detailing how each element kickstarts an immune response against the tumours. Workenhe, who is a trained veterinarian and a virologist, is now applying these findings to further study immune responses and inflammatory cell death in tumours.

“A lot of people are excited about engineering viruses to inflame the tumour and improve cancer treatment,” says Workenhe. “The implications of these findings for human cancer therapy may be huge.”

This post was adapted from a University of Guelph news story.

November 25, 2020

Cancer research through COVID: A drug discovery student’s perspective

Despite disruptions, cancer researchers across Ontario are continuing to make scientific progress in labs and at home. Here, Vivian discusses her master’s project, discovering drug targets for future immunotherapies.

November 17, 2020

Towards healthier lives for childhood leukemia survivors

Dr. Brian Nieman takes a deep dive into the neurocognitive side effects of childhood leukemia treatment seeking new ways to improve the lives of survivors

Due to advances in the treatment of childhood acute lymphoblastic leukemia (ALL), more than 90 per cent of children diagnosed with the disease will live long and relatively healthy lives. However, there are still long-term neurocognitive side effects – or lasting effects – of treatment including attention, processing speed and motor coordination difficulties. Investigating these lasting effects at The Hospital for Sick Children (SickKids) is Dr. Brian Nieman, who is committed to further improving the lives of childhood leukemia survivors.

Recently published in Neuroimage: Clinical and Pediatric Research are two of Nieman’s latest studies on the neurocognitive impact of ALL treatment on growing children. In these studies, Nieman and collaborators discovered that many leukemia survivors have neurocognitive abilities that are comparable to other children but on average survivors are doing worse than their peers.

Dr. Brian Nieman.

“We see that leukemia treatment has broad and lasting implications on the brain,” says Nieman, OICR Investigator and Senior Scientist at SickKids. “Determining when these key changes occur and which part of a child’s treatment is causative will be an important step in designing protective or rehabilitative strategies in the future.”

The study that was published in Neuroimage: Clinical was the first to investigate the impact of ALL treatment on the brains of survivors ages 8-18 using MRI. The study found extensive structural differences in the brain between survivors and their peers. The study published in Pediatric Research focused on quality of life measures, and identified the impact of leukemia treatment on IQ, behavioural measures, attention and cognitive abilities.

With this new knowledge and Nieman’s expertise in experimental mouse model imaging, he and collaborators are now investigating which chemotherapy drugs cause these lasting effects and when these developmental changes are occurring in a leukemia patient’s development. They strive to identify new strategies to protect and rehabilitate the developing child’s brain.

“Over the last few generations, we’ve seen childhood leukemia survival reach 90 per cent. Over the last few decades, we’ve seen a shift in practice that has allowed patients to experience fewer side effects. But these studies demonstrate that treatment isn’t ideal yet,” says Nieman. “The results that we’ve collected suggest that we could potentially help many leukemia patients and we’re committed to do so.”

November 4, 2020

Trove of patient-reported data offers path to improve cancer symptom management

OICR-supported research study investigates the symptoms experienced by patients undergoing lung cancer treatment using a decade’s worth of data

In 2010, the Edmonton Symptom Assessment System (ESAS) was rolled out in all cancer centres in Ontario to improve cancer symptom management. ESAS allows patients to self-report on the severity of nine common cancer-associated symptoms throughout their treatment, enabling their care team to better monitor symptoms in real time. The data from the initiative was collected in a central repository over the past decade and now Drs. Natalie Coburn and Alexander Louie, among other researchers, are tapping into the data to study how lung cancer patients feel and how their symptoms are managed.

Dr. Natalie Coburn.

“This initiative represents a shift towards greater focus on symptoms of cancer and patient quality of life,” says co-lead investigator Dr. Natalie Coburn, Senior Scientist in Evaluative Clinical Sciences and Surgical Oncologist at Sunnybrook’s Odette Cancer Centre. “We believe that improving symptom management through cancer care is important, not only for supporting the patients themselves, but also for building a more efficient and effective healthcare system.”

Through their preliminary analyses, they’ve discovered key insights that may help guide their future research into lung cancer symptom management. They observed that symptoms often improve over the course of treatment but worsen late in disease progression. Early results also debunk the common misconception that nausea is a universal and pervasive side effect of chemotherapy treatments. The thought of having severe nausea can cause stress for a lot of patients, but knowing it may not be as severe as they think can be a big deciding factor when clinicians discuss their choices of care. They found that tiredness and fatigue are often much more common than nausea, but symptoms are generally not as severe as patients expect.

Dr. Alexander Louie.

“With this real-world dataset, we can focus in on exactly when patients are feeling worse and find new ways to help patients feel better throughout treatment,” says co-lead Dr. Alexander Louie, Scientist in Evaluative Clinical Sciences and Radiation Oncologist at Sunnybrook’s Odette Cancer Centre. “Our research is helping discover new areas of improvement so that ultimately, we can develop and implement interventions to better support symptom management.”

The research team is now in the process of meeting with patient groups and collaborators to establish priorities for future analyses.

“We have a strong, multi-disciplinary team working on this initiative including clinicians, analysts and patients who each bring their own expertise to the table,” says Victoria Delibasic, a lead Research Coordinator of the team. “We’re proud that this research is empowering the community to help people with cancer thanks to the real-world data from those who have lived through similar experiences.”

October 15, 2020

OICR team awarded $300,000 to expand cancer research software tools for more researchers, new disease applications and greater impact

OICR’s Genome Informatics team receives federal funding from Canada’s National Research and Education Network to expand Overture, an open-source software suite for big data genomic research

Software tools are key to turning big data into discoveries in science and medicine. Reusing existing software accelerates the pace of discovery and can maximize the impact of public funding for research but only if the software is accessible and useable.

Today, Canada’s National Research and Education Network, CANARIE, announced their support of 12 teams across Canada as they adapt their existing research platforms for re-use by other research teams. With this funding, the OICR Genome Informatics team will evolve the accessibility and functionality of Overture, their software suite for big data genomic research.

“Our team has a longstanding commitment to the community,” says Dr. Christina Yung, Director of Genome Informatics. “We want to maximize the impact with the resources we have, which means focusing on key challenges and making our tools the most useful for the research community. This funding will allow us to do just that.”

Overture is a software suite of customizable and extendable tools for big data genomic research. One of Overture’s key products allows research teams to store and distribute genomic datasets while providing an authentication and authorization system for secure and safe data sharing. Overture also provides user-friendly portals for browsing and querying data, which was developed as part of the International Cancer Genome Consortium (ICGC) and the European-Canadian Cancer Network (EUCANCan).

CANARIE’s support will allow OICR’s team to simplify Overture installation and configuration, provide additional authentication functionality and improve the customizability of the data portal.

“With this support, we will add new features to increase adoption by new research teams,” says Yung. “The hope is to enable research teams from across Canada and around the world to re-use the software that we developed and accelerate their own discoveries. We’re grateful for how the community has contributed to our research through sharing open-source software and we’re proud to give back.”

“The ability to connect, share data and work collaboratively with researchers from across Canada and the world is a priority for our government,” said the Honourable Navdeep Bains, Minister of Innovation, Science and Industry [link to release]. “Today’s funding will help accelerate Canadian discoveries by making it easier for our researchers to find, access, and reuse data with collaborators across the country and around the world.”

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

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