February 26, 2021

Drug combination results in longer survival for patients with recurrent and advanced ovarian cancer

Dr. Stephanie Lheureux and Dr. Amit Oza
Dr. Stephanie Lheureux | Dr. Amit Oza

An OICR-supported research team at the Princess Margaret Cancer Centre has shown that adding a targeted drug to chemotherapy results in longer survival and a stronger response to treatment in a difficult-to-treat form of ovarian cancer.

When a patient’s ovarian cancer becomes resistant to treatment, the patient has few alternative options and faces an estimated survival of less than 18 months. This is a reality for approximately one in four women with the disease.

Against this challenge, a team OICR-supported through OICR’s Ovarian Cancer Translational Research Initiative (TRI), headed by Dr. Stephanie Lheureux, Princess Margaret (PM) Clinician Investigator and Dr. Amit Oza, PM Senior Scientist and OICR TRI leader, led a Phase II clinical trial including nearly 100 women across 11 centres to evaluate the combination therapy of adavosterib and gemcitabine. Their discoveries, which were recently published in The Lancet, demonstrated that this combination increased survival by 4.3 months relative to chemotherapy and placebo alone. 23 per cent of patients’ cancers responded to the chemotherapy, in contrast to a 6 per cent response rate seen using chemotherapy alone.

“By combing two drugs, we were able to change the trajectory of cancer for a high-risk group of women with advanced disease who did not have many choices left,” says Oza, Medical Director of the Cancer Clinical Research Unit and Co-Director of the Bras Drug Development Program at Princess Margaret Cancer Centre. “That is significant.”

Lead author Dr. Stephanie Lheureux says that the study provides a signal of hope for women with ovarian cancer who develop drug-resistance to treatment. The study included some women who had received up to eight different previous treatments which had stopped working.

“As we learn more and more about the biology of tumours, we can target treatments more precisely to the molecular changes in a cancer to improve the type and response of our treatments. That will change outcomes for patients,” says Lheureux, who is also the Princess Margaret Site Lead for Gynecological Oncology. “I want our patients to know there is hope to find better treatment to control their cancer.”

By combing two drugs, we were able to change the trajectory of cancer for a high-risk group of women with advanced disease who did not have many choices left

Dr. Amit Oza

The study participants had high-grade serous ovarian cancer – the most malignant form of ovarian cancer, accounting for up to 70 per cent of all ovarian cancer cases. They were randomly assigned to receive either adavosertib plus gemcitabine (chemotherapy) or placebo plus gemcitabine.

The patients’ tumours were biopsied before and during treatment to assess the effectiveness of the drug regimens. Analysis of genetic mutations and changes in DNA damage response pathways was performed by the Joint Genomics Program at OICR and the Princess Margaret Cancer Centre.

“This discovery underscores the importance of bringing scientists and clinicians together to tackle difficult questions from different perspectives to offer new insights into the biology of cancer,” says Dr. Laszlo Radvanyi, President and Scientific Director, Ontario Institute for Cancer Research. “It shows how we can push these damaged cancer cells right smack into mitotic catastrophe to their demise. This clinical trial has validated good science that has begun to uncover how a cancer cell’s own DNA repair mechanism can be used against it and capitalizes on this unique vulnerability by combining drugs in a smart way. The small-molecule DNA repair inhibitors used in this study targeting the G2-M checkpoint hold great promise as chemotherapy enhancers by further damaging and ultimately destroying tumour cells, thereby overcoming treatment-resistant ovarian cancer.”

In addition to improving overall survival by 4.3 months, the combination of adavosertib and gemcitabine improved progression-free survival by 1.6 months relative to chemotherapy alone.

“Taken together, these three outcomes give us a strong signal that we can potentially improve survival for these patients who face bleak prospects,” says Dr. Oza, adding that the study carefully co-ordinated patients with similar genomic backgrounds with a targeted drug that exploits a defect in cancer cells.

“This is precision medicine at its best,” he adds. “This is how we will develop better treatments for our patients.”

Through whole-exome sequencing, the study found that patients’ tumours acquire several changes – or mutations – that play an important role in regulating critical cell cycle checkpoints. These mutations could disable these “quality control” checks, allowing cancer cells with damaged DNA to continue dividing and growing unimpeded.

Further, they discovered that the drug adavosertib could effectively target tumour cells that harbour the key TP53 mutation.

“We exploited a fatal flaw in cell division, diverting and stopping the damaged cells from growing into a tumour,” explains Lheureux. “We showed the potential of targeting the cell cycle in a specific subgroup of patients with highly resistant ovarian cancer. This opens up new avenues of treatment possibilities.”

The research group now plans to evaluate the impact of this combination on patients’ quality of life and analyze patients’ blood samples to search for blood-based indicators of treatment resistance.


In addition to OICR’s support, the study was also funded by the Princess Margaret Cancer Foundation, the U.S. National Cancer Institute Cancer Therapy Evaluation Program, the U.S. Department of Defense Ovarian Cancer Research Program, and AstraZeneca.

February 23, 2021

Premier Doug Ford visits OICR

Doug Ford and Trevor Pugh

On February 23, Ontario Premier Doug Ford visited MaRS and included a stop at OICR to learn about how the Institute is using its expertise in genomics and other areas to contribute to COVID-19 research. Premier Ford was accompanied by MPPs Donna Skelly and Nina Tangri, who are Parliamentary Assistants to the Minister of Economic Development, Job Creation and Trade, Vic Fedeli.

During the visit Premier Ford met with members of OICR and FACIT leadership and was then given a demonstration of some of OICR’s COVID-19 research by Dr. Trevor Pugh, Director of the OICR-Princess Margaret Cancer Centre Joint Genomics Program.



Premier Ford also spoke to reporters during his visit and conveyed his thanks and support for OICR’s research into both cancer and COVID-19. “These are the areas that Ontario wants to invest in to lead the world in research, not only in COVID but in cancer and other diseases…We are very grateful for all the folks here.”

Read more about OICR contributions to COVID-19 research.





February 19, 2021

OICR-supported collaboration discovers new method to stunt the growth of brain cancers

Inhibiting a key enzyme could help stop the growth of glioblastoma

Fewer than 10 per cent of people diagnosed with glioblastoma will survive beyond five years. Despite advances in understanding this deadly brain cancer, therapy options for this disease are severely limited. In a study recently published in Nature Communications, researchers have discovered that inhibiting a key enzyme, PRMT5, can suppress the growth of glioblastoma cells. Their findings demonstrate a novel approach to treating the disease, paving the way for a new class of therapeutics.

Dr. Peter Dirks, co-leader of OICR’s Brain Cancer Translational Research Initiative.

A multidisciplinary team with expertise in cancer stem cells, protein structures, small molecule development and multi-omic analyses enabled this discovery. The group, was co-led by Dr. Peter Dirks, Senior Scientist and Neurosurgeon at the Hospital for Sick Children (SickKids) and co-leader of OICR’s Brain Cancer Translational Research Initiative along with researchers at the Princess Margaret Cancer Centre, the Structural Genomics Consortium (SGC) and the University of Toronto. Many of the researchers involved in the study are also part of the Stand Up To Cancer (SU2C) Canada Cancer Stem Cell Dream Team, which receives support from OICR.

Through the study, they showed that inhibiting PRMT5 affected a large network of proteins that are important in cell division and growth, triggering cell senescence, and stopping the unrelenting division of cancer cells.

While PRMT5 inhibition has been previously suggested as a way to target brain and other cancers, no one has tested this strategy in a large cohort of patient tumour-derived cells that have stem cell characteristics, cells that are at the roots of glioblastoma growth.

They found that specific molecules – precursors to actual therapeutic drugs – inhibited the same enzyme, PRMT5, stopping the growth of a large portion of these patient-derived cancer stem cells. Many current drugs do not eliminate cancer stem cells, which may be why many cancers regrow after treatment.

“We used a different strategy to stop cancer cells from proliferating and seeding new tumours,” says co-senior author, Dr. Cheryl Arrowsmith, Senior Scientist at the Princess Margaret Cancer Centre who leads the University of Toronto site of the SGC. “By inhibiting one protein, PRMT5, we were able to affect a cascade of proteins involved in cell division and growth. The traditional way of stopping cell division has been to block one protein. This gives us a new premise for future development of novel, more precise therapies.”

“This strategy also has the opportunity to overcome the genetic variability seen in these tumours,” says co-senior author, Dirks, who also leads the SU2C Canada Dream Team. “By targeting processes involved in every patient tumour, which are also essential for the tumour stem cell survival, we side-step the challenges of individual patient tumour variability to finding potentially more broadly applicable therapies.”

The researchers also examined the molecular features of the patient-derived glioblastoma cells by comparing those that responded well to those that did not respond as well. They found a different molecular signature for the tumour cells that responded. In the future, this could lead to specific tumour biomarkers, which could help in identifying those patients who will respond best to this new class of drugs.

The research group will continue testing PRMT5 inhibitors to develop new therapies for people with glioblastoma.

“Right now, we have too few medicines to choose from to make precision medicine a reality for many patients,” says Arrowsmith. “We need basic research to better understand the mechanism of action of drugs, particularly in the context of patient samples. This is what will help us develop the right drugs to give to the right patients to treat their specific tumours.”

The research group also included OICR-affiliated scientists and staff researchers, Drs. Trevor Pugh, Mathieu Lupien, Benjamin Haibe-Kains, and Ahmed Aman.

Adapted from a SickKids news release.

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 4, 2021

OICR-supported clinical trial leads to practice-changing results for men with prostate cancer

Multidisciplinary research group demonstrates that using MRI and targeted biopsies can avoid unnecessary prostate biopsies in a third of men and reduce the diagnosis of insignificant cancers

Determining whether a patient with prostate cancer requires aggressive therapy or active surveillance is a challenge. Current tests can detect early signs of prostate cancer, but these tests can lead to many unnecessary and painful biopsies for patients whose disease never becomes aggressive.

In an OICR-funded Phase III clinical trial, researchers have found that using Magnetic Resonance Imaging (MRI) and MRI-guided biopsies as needed, can reduce the number of unnecessary prostate biopsies and the diagnosis of insignificant cancers. The study results were recently published in JAMA Oncology.

The study, called the Prostate Evaluation for Clinically Important Disease: MRI vs Standard Evaluation Procedures (PRECISE), included 453 participants at cancer centres across Canada who were assigned to either the current standard of care – a systematic transrectal ultrasound-guided (TRUS) biopsy – or a new method – MRI with MRI-guided biopsy as needed.

The study demonstrated that using MRI and MRI-targeted biopsies caught clinically significant cancers as effectively as conventional TRUS biopsies, but reduced the rate of men undergoing biopsy by almost 40 per cent. The MRI method also halved the number of unnecessary diagnoses of slow growing, clinically insignificant cancers. Additionally, those who did have biopsies in the MRI arm had significantly fewer samples taken relative to those in the TRUS biopsy arm, meaning fewer needles and less pain and discomfort for patients.

Dr. Greg Pond

These clinical data show the revolutionary impact of the use of prostate MRI in cancer diagnosis and surveillance.

“Approximately one in eight men will be diagnosed with prostate cancer in their lifetime,” says the study’s lead statistician and OICR Investigator, Dr. Greg Pond, who is also an Associate Professor at McMaster University and Senior Biostatistician at the Ontario Clinical Oncology Group. “These clinical data show the revolutionary impact of the use of prostate MRI in cancer diagnosis and surveillance.”

Dr. Masoom Haider

“Using our current standard methods, we recognize that we are overdiagnosing some prostate cancers, leading to unnecessary biopsies and treatments,” says co-lead of the study, Dr. Masoom Haider, Head of the Radiomics and Machine Learning Research Lab at the Lunenfeld-Tanenbaum Research Institute, Professor at the University of Toronto, and OICR Clinician Scientist. “Through PRECISE, we’ve demonstrated that using MRI and MRI-targeted biopsies as an alternative to standard biopsies, can effectively detect clinically significant cancers, but avoid overdiagnosing clinically insignificant cancers. This means reducing the number of needles or eliminating biopsy altogether if a patient doesn’t need it. For our health system, this alternative may present an opportunity to use our resources more effectively.”

Haider has played a leading role in integrating the PRECISE findings into Cancer Care Ontario (CCO) guidelines for prostate cancer management. The study’s findings influenced CCO’s Prostate MRI Guideline 27-2 and will be implemented this year, meaning more prostate cancer patients across Ontario may be spared unnecessary biopsies and treatment thanks to MRI and MRI-targeted biopsies.

Read the news release

February 4, 2021

Clinical trial: Using MRI for prostate cancer diagnosis equals or beats current standard

Phase III clinical trial of men with a clinical suspicion of prostate cancer finds MRI with targeted biopsies to be more accurate at diagnosis and less intrusive than current standard

Toronto – (February 4, 2021) The results of a Phase III randomized clinical trial have shown that when it comes to detecting clinically significant prostate cancer, Magnetic Resonance Imaging (MRI) with targeted biopsies (MRI-TBx) matches the current standard and brings a multitude of advantages. The PRostate Evaluation for Clinically Important Disease: MRI vs Standard Evaluation Procedures (PRECISE)study will help to make prostate cancer diagnosis more accurate and less invasive.

PRECISE included 453 participants at Canadian academic cancer centres who were either assigned to receive MRI imaging followed by MRI-TBx of suspicious areas (identified by MRI), or the current standard of care of a systematic 12-core transrectal ultrasound-guided (TRUS) biopsy (TRUS-Bx).

Key findings:

  • MRI with targeted biopsy found five per cent more clinically significant prostate cancers compared to those receiving systematic TRUS-Bx biopsies, conclusively demonstrating the method can at least match the performance of the current standard of care.
  • Compared to standard TRUS-Bx, the MRI-TBx were found to be better in identifying clinically significant cancers.
  • More than a third of patients in the MRI arm of the trial avoided biopsies altogether following negative imaging results. Those individuals received a follow-up MRI in two years’ time.
  • Those who did have biopsies in the MRI arm had significantly fewer samples taken when compared to systematic TRUS-Bx, resulting in less pain and discomfort for patients. Moreover, the MRI arm had a decreased adverse event profile, including less hematuria (blood in the urine) and incontinence.
  • There is a major unmet need for a test that identifies clinically significant prostate cancer while avoiding overdiagnosing clinically insignificant cancers. Use of MRI reduced the unnecessary diagnosis of slow growing, clinically insignificant prostate cancers by 55 per cent.

These findings show decisively that MRI together with targeted biopsies offer patients a less invasive procedure, the chance to avoid a biopsy all together and can help avoid the over-treatment of clinically insignificant prostate cancer – all while detecting a higher rate of clinically significant cancers.

“My colleagues and I are thrilled about these results that show, without a doubt, that imaging and targeted biopsies are the future of prostate cancer diagnosis. We can catch more of the cancers we should be treating, avoid unnecessary treatment at the same time and improve the quality of life for our patients.” says Dr. Laurence Klotz, Chair of Prostate Cancer Research at Sunnybrook Health Sciences Centre and lead author of the study. “We thank the study participants and our funders for their support and look forward to continuing our efforts to have this technology used more widely.”

“The study’s findings have influenced Ontario Health-Cancer Care Ontario’s upcoming, updated Prostate MRI Guidelines, which will be released this year,” says Dr. Masoom Haider, co-lead of the study and Professor of Medical Imaging at the University of Toronto, and Clinician Scientist with the Ontario Institute for Cancer Research (OICR). “I am pleased to see our research produce results that will make a real difference in how prostate cancer is diagnosed and improve the lives of patients.”

“I congratulate Dr. Klotz and the PRECISE team on this truly impactful research which will change clinical care and make a difference for men with prostate cancer,” says Dr. Christine Williams, Deputy Director and Head, Clinical Translation, OICR. “It is a great example of how, with our partners, we are moving research innovations to the clinic to improve the lives of patients and treat cancer with improved precision.”

“These practice-changing results will have a significant and positive impact on the roughly 64 Canadians who are diagnosed with prostate cancer every day. Thanks to the efforts of Dr. Klotz and his team, people will need to undergo fewer biopsies and for some of them, they will be spared from unnecessary biopsies and treatments altogether,” says Dr. Stuart Edmonds, Executive Vice President, Mission, Research and Advocacy at the Canadian Cancer Society. “We are proud to support this research, which will help people with prostate cancer live longer, fuller lives.”

“At Movember, we are honoured to play a role in funding cutting-edge research like the PRECISE study, ultimately helping to provide more positive outcomes for men living with or beyond a prostate cancer diagnosis,” says Todd Minerson, Country Director for Movember Canada.  

PRECISE was funded by the Canadian Cancer Society with funds provided by Movember and by the Ontario Institute for Cancer Research.

About the Ontario Institute for Cancer Research

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.

About the Canadian Cancer Society

The Canadian Cancer Society (CCS) is the only national charity that supports Canadians with all cancers in communities across the country. No other organization does what we do; we are the voice for Canadians who care about cancer. We fund groundbreaking research, provide a support system for all those affected by cancer and shape health policies to prevent cancer and support those living with the disease.

Help us make a difference. Call 1-888-939-3333 or visit cancer.ca today.

About Movember

Movember is the leading charity changing the face of men’s health on a global scale, focusing on mental health and suicide prevention, prostate cancer and testicular cancer. The charity raises funds to deliver innovative, breakthrough research and support programs that enable men to live happier, healthier and longer lives. Committed to disrupting the status quo, millions have joined the movement, helping fund over 1,250 projects around the world. In addition to tackling key health issues faced by men, Movember is working to encourage men to stay healthy in all areas of their life, with a focus on men staying socially connected, and becoming more open to discussing their health and significant moments in their lives. The charity’s vision is to have an everlasting impact on the face of men’s health. To donate or learn more, please visit Movember.com.

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.

February 3, 2021

Imagining the next 20 years and planning for the next five

How OICR is using strategic foresight to prepare for the future and inform its 2021-2026 Strategic Plan

OICR focuses on translating cancer research discoveries and transforming cancer care. Achieving this mission, however, is dependent on a myriad of factors beyond scientific research and development. Social, political, technological, economic and environmental factors all may play a role in driving the future of cancer research and care in Ontario and beyond.

As part of the process to develop its 2021-2026 Strategic Plan, OICR partnered with Dr. Peter Bishop, Professor Emeritus at the University of Houston, professional futurist and President of Strategic Foresight and Development, to investigate the possible futures of cancer research and care in Ontario and around the world. OICR plans to launch the 2021-2026 Strategic Plan in April 2021.

Read the full report in Foresight.

With the help of leaders from research institutes, hospitals and the public sector across Ontario, 20 key drivers were identified that may significantly affect the future of cancer, including an aging population, innovations in quantum computing and the growing focus on holistic health. The group then designed and evaluated potential future scenarios and derived four main insights that were used to inform OICR’s 2021-2026 Strategic Plan:

Data dilemmas
While health-related datasets continue to grow and new sources of data emerge, standards around data gathering, monitoring, integration, sharing and implementation remain unclear. These parameters affect how the cancer community implements precision medicine for people living with cancer. Through its 2021-2026 Strategic Plan, OICR’s computational biology and informatics research programs will continue to develop essential data tools and apply responsible data sharing standards, while strengthening Ontario’s global leadership in health data integration and federation through initiatives such as the Global Alliance for Genomics and Health, the International Cancer Genomics Consortium Accelerating Research in Genomic Oncology, Canada’s Digital Health and Discovery Platform, and the Ontario Data Integration Network.

Powerful patients
Integrating the perspectives of patients into research is becoming increasingly important to ensure that research ultimately leads to patient benefit. Over the next few decades, patients will increasingly have access to more information and misinformation, challenging the research and health communities to ensure patients receive the information they need to make informed decisions. To address these challenges, OICR will foster and grow meaningful partnerships with patients and caregivers to integrate patient values into OICR priorities. OICR is currently developing a Patient Family Advisory Council, which will advise on OICR’s patient partnership initiatives.

Funding fragility
As the cost and urgency of cancer drug development continue to increase, alternative funding for research and translation may become necessary. This challenge has become more apparent as the world looks to recover from the socio-economic impacts of the coronavirus pandemic. OICR will continue to strengthen partnerships within the cancer ecosystem over the next five years, to attract further investment in cancer research and innovation to Ontario. OICR will also build health services research expertise into critical research programs to evaluate the costs and benefits of emerging interventions to support the path between discovery and patient care.

Teetering trust
Trust between stakeholders in the cancer system – including patients, families, researchers and clinicians – is critical to progress in cancer research. Trust is imperative to data gathering, sharing and processing, and these data are necessary to make cancer detection and treatment more precise. Through the 2021-2026 Strategic Plan, OICR aims to work together with partners to ensure we remain and become an even more trusted custodian of patient data and scientific information to support high quality translational research, bridging the lab to the clinic.

“Our mission is based on translating cancer research discoveries to transform cancer care,” says Dr. Rebecca Tamarchak, Senior Director of Strategic Planning and Governance. “Integrating foresight into our strategic planning process is our way to proactively anticipate the future in order to develop a nimbler strategy.”

The strategic foresight workshop, which was hosted in late 2018, kicked off OICR’s multi-phase strategic planning process. The process, led by Tamarchak and OICR’s President and Scientific Director, Dr. Laszlo Radvanyi, has incorporated insights from extensive consultations with OICR staff, collaborators and the community.

“This strategic foresight study has reinforced the importance of enduring partnerships across the cancer research community and we look forward to strengthening those relationships over the next five years to maximize our impact on cancer patients and the Ontario economy,” says Tamarchak. “We’re excited to bring the 2021-2026 Strategic Plan into action.”

February 3, 2021

What we learned at the recent OICR-JLABS cell therapy symposium

OICR and Johnson & Johnson Innovation – JLABS @ Toronto launch the OICR-JLABS Cancer Symposium Series, featuring leaders, innovators and trail blazers in cell therapy

On January 28, OICR and JLABS @ Toronto hosted the inaugural symposium of their Cancer Symposium Series, focused on horizons and controversies in cell therapy for cancer treatment. Invited speakers from around the world took a deep dive into the promise of gene therapy and the key challenges that they’re working to overcome.

The event was hosted by the Regional Head of JLABS Canada, Allan Miranda, and OICR’s President and Scientific Director, Dr. Laszlo Radvanyi. Guest speakers included Dr. James Yang from the National Cancer Institute, Dr. Emily Titus, Vice President at Notch Therapeutics, and Dr. Michael Maguire, CEO of Avectas.

Event recap

  • Dr. Yang reviewed the notable advancements made in Adoptive T cell Therapy (ACT) for certain cancers, like melanomas. Despite these advancements, he emphasized the importance of further research since most of the common cancers that kill people have yet to be addressed using immunotherapy. His presentation outlined some key scientific and biological challenges in developing effective ACT for epithelial cancers, highlighting that epithelial cancers, which represent the vast majority of cancer cases, have a lower mutational burden relative to melanomas, often have a limited number of tumour-infiltrating lymphocytes, and are difficult to mimic in experimental models.
  • Dr. Titus presented Notch Therapeutics’ platform for generating T cells and other immune cells from stem cell lines. The team at Notch, which has expanded from Toronto to Vancouver and Seattle, is leveraging their platform to build a pipeline of sophisticated T cell therapeutic products.
  • Dr. Maguire shared Avectas’ automated GMP engineering platform, SOLUPORE, which is built to enable the ex-vivo manufacture of gene modified cell therapy products. He emphasized the importance for improved complex engineering solutions to address solid tumours.

The event highlighted the potential of cancer cell therapy and the technologies that will advance the field of cell therapy in the future. The event recording can be accessed here.

If you would like OICR event invitations and news delivered directly to your inbox, please subscribe here.

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.

January 8, 2021

Q&A with new OICR Investigator Dr. Shraddha Pai on uncovering the hidden differences between cancers

OICR is proud to welcome Dr. Shraddha Pai to its Computational Biology Program as a Principal Investigator. Here, Pai discusses current challenges in understanding diseases and what motivates her to tackle some of the biggest challenges in biomedical research.

What are some of the research questions you’re interested in?

I’m very driven to understand why different people with the same cancer type, have different outcomes and respond differently to the same treatment. As genomic assays get cheaper, we learn more about molecular interplay in different cells, and our population datasets become larger and mature, we are able to integrate different layers of the genome and cell types, to try to get at this question. For example, we now believe there are four main types of medulloblastoma with different underlying molecular networks and outcomes. This field of research is called ‘precision medicine’: using patient profiles to match them with the most effective treatment. But really this is just a new phrase to describe what doctors have been doing since the dawn of medicine; it just means that now we’re using powerful computers and algorithms to find patterns in much larger and complex genomic datasets. The principle is the same.

As a trainee in Dr. Gary Bader’s group, I led the development of an algorithm that integrates several types of patient data to classify patients by outcome.  Our method – called netDx – adapts the idea of recommender systems, used by Netflix and Amazon, to precision medicine. Just as one would ask Netflix to “find movies like this one”, netDx helps identify patients “with a treatment profile like this”. In a benchmark, netDx out-performed most other methods in predicting binary survival in four different types of cancer. Importantly, netDx is interpretable, and recognizes biological concepts like pathways. This makes it a useful tool to get mechanistic insight into why a predictor is doing well, and provides a way to understand the underlying biology and perhaps drive rational drug design.

I also have a special interest in understanding the link between epigenetics and disease, particularly as this pertains to the brain. Epigenetics refer to molecular changes that change how the genome behaves – for example, turning a gene on or off in a given cell type. My own previous research in mental illness has found epigenetic biomarkers related to psychosis, which explain the distinctive features of this condition. The same may be the case in certain types of cancers, particularly those of developmental origin.

How do you plan to unravel these complex layers of biology?

My research program has two main goals. The first is to build models for precision medicine – predicting disease risk, treatment response – starting with population-scale datasets that have several types of patient data. I’m hoping to use existing and emerging data such as UK BioBank, CanPath, ICGC-ARGO and the Terry Fox Research Institutes’ datasets, and ongoing clinical trials, to identify which clinical outcomes are easily amenable to our approaches. The models my group builds will incorporate prior knowledge about genome organization and regulation, so that these are interpretable. For example, we will use epigenomic maps of specific tissue types, or data from single-cell resolution maps, pathway information, to find and organize relevant needles in the genomic haystack. This feature will give us interpretability, which is key to increasing confidence in a model, as well as to improving the understanding of cellular pathways that affect disease and eventual drug development.

My second goal is to understand the epigenomic contributions – particularly developmental changes – to cancer risk, using a combination of molecular biological, genomic and analytic techniques.

As I work toward these goals, I hope to collaborate on complementary projects, such as identifying DNA methylation changes in circulating tumour DNA and improving how we subtype adult tumours. These projects will hopefully lead to new biomarkers, and ultimately improvements to how we diagnose and treat cancer.

Importantly, the software that my team builds will also be openly available to the research community, so others can apply my methods to different types of diseases. I’m excited to get started.

Your work applies beyond cancer. How do you traverse these different disease areas?

The reclassification of disease based on molecular or other biomarkers, and how disease subtype affects risk and treatment response, isn’t unique to cancer – the same research questions extend to other types of disease such as metabolic diseases, autoimmune diseases and mental illness. At the end of the day, we are looking at the same system organized at the molecular, cellular and organ-level, with similar principles of genomic regulation and perhaps similar considerations for drug discovery. Our algorithms are based on these general principles and can therefore be used to answer similar questions for different disease applications, or very different types of cancer. Of course, it’s important to collaborate with teams that have domain expertise to make sure the algorithms are “fine-tuned” for a particular application, and I look forward to benefitting from those partnerships.

What excites you about this type of work?

I’m excited to join a community where basic research is so strongly connected to clinical purpose. Personally, I am very motivated by the prospect of a positive impact on patients within my lifetime and feel that my group’s work is more likely to have a valuable impact in an environment that combines basic and translational research. That said, we’re only just beginning to see the benefits of precision medicine and many challenges remain to bring genomic knowledge into practice. I hope that I can create more useful methods and models for precision medicine and improved clinical decision-making in the coming decade.

I’m especially excited to be at OICR because of the Institute’s access to clinical trials, strong genomics and computational biology program, and pharmacology team. If my group can find promising biomarkers and leads, we can work with OICR collaborators in the Genomics and Drug Discovery groups to move from basic research to application.

Read more about Dr. Shraddha Pai.

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.”

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