April 15, 2021
A new study has looked at the effects of bans on menthol cigarettes after two years across seven Canadian provinces and found that once in place, 58.7 per cent of menthol smokers attempted to quit compared to 49 per cent in non-menthol smokers. The study was conducted by the International Tobacco Control Policy Evaluation Project (the ITC Project), which is led by Dr. Geoff Fong, OICR Senior Investigator and Professor at the University of Waterloo.
The study, published in the journal Tobacco Control, also found that those who smoke menthols daily were nearly twice as likely to attempt to quit as daily non-menthol smokers – 21 vs. 11.6 per cent. Also, menthol smokers who had quit before the ban were much less likely than non-menthol smokers to relapse. The study used a national sample of 1,098 non-menthol and 138 menthol smokers participating in the ITC Canada Smoking and Vaping Survey, who were surveyed both before the menthol ban (in 2016) and after the menthol ban (in 2018).
Menthol flavoured cigarettes create a cooling effect that numbs the harshness of cigarette smoke, which helps draw in and keep new smokers, especially young people. They are also of concern to public health experts in the U.S., where 85 per cent of menthol cigarette smokers are African American. As a result, that community has felt much greater harms from menthol cigarette use. Fong and other experts have continued to call for a ban in the U.S.
“Our study demonstrates the substantial benefits of banning menthol cigarettes,” says Fong. “The enormous success of the Canadian menthol ban makes it even clearer now that the U.S. should finally ban menthol, which the tobacco industry has used for decades to attract new smokers and to keep many of them as customers, especially among the African American community.”
“The positive effects of the Canada menthol ban suggest that a U.S. menthol ban would lead to greater benefits since menthol cigarettes are much more popular in the U.S. From our findings, we estimate that banning menthol cigarettes in the U.S. would lead an additional 923,000 smokers to quit, including 230,000 African American smokers.”
March 30, 2021
Antonia Palmer, Chair of OICR’s Patient and Family Advisory Council, shares her thoughts from the Conference
OICR recently established a Patient and Family Advisory Council (PFAC). The PFAC will be the chief patient-focused advisory body for the Institute and will have a critical role in helping it become a patient-partnered organization. PFAC members are an engaged and impressive group of patients and patient representatives from across Ontario. I have the great honour of taking the role of the first Chair of the PFAC and look forward to what our group will be able to accomplish as the group becomes established within OICR.
The first day of the OICR Translational Research Conference has been extremely interesting and illuminating. We applaud the future vision for OICR that Dr. Laszlo Radvanyi, the Institute’s President and Scientific Director, described in his opening remarks – placing an important focus on the early detection of cancer and on the development of precision tailored treatments leading to the cure of different cancer types and improved monitoring.
We are seeing research that is extending across different cancer types. Research into early detection that is simultaneously effective, minimally invasive, and cost effective. The creative design of clinical trials such as the Window of Opportunity (WOO) clinical trials, also known as phase 0 clinical trials, that evaluate new treatment strategies in between the time of a patient’s cancer diagnosis and their surgery. During the sessions we were informed about research into molecular signalling and how disruptions into signalling pathways contribute to disease, how radiopharmaceuticals are used for targeted therapies and imaging – working to improve the dynamic monitoring of disease and for early detection and diagnosis, and research into methods of cell protection and how to override checkpoints to disrupt inhibition. In the keynote address from Dr. Sylvia Plevritis, we learned more about the tumour microenvironment interactome.
When patient partners involved in the Conference had a debrief earlier today, we talked about the significant importance of collaboration between researchers, research institutions, within Ontario, other provinces and across Canada. Sharing findings and information in conferences like this one is absolutely critical but we must develop more regular, accepted and seamless ways of sharing research and patient information within provinces and across the country. Data sharing is critical for moving the science forward and an example of this was specifically highlighted in the talk earlier today on hereditary cancers and being able to share information about patients in one family who live in different locations. We must continue to work to address communication and data sharing silos to create more opportunities for data sharing. The pandemic has also been a spotlight for this important issue.
Patient partners involved in the Conference greatly appreciate the lay summaries for presentations, the ability to ask questions, and to be a part of better understanding the immense breadth of work that is being done in the world of cancer and how OICR is a part of making a difference in oncology.
To all the researchers providing formal presentations, presenting posters, asking questions, and immersing themselves in science – patient partners see you, your work, passion and dedication. We are pleased to be able to learn from you and hope that we can create more pathways where you can learn from us. Your work gives us hope, and for that, we thank you.
The involvement of patient partners in research provides for some rich interactions and learnings that can occur in the design, execution and communication of findings. Patient partners are different from research participants – they are people with lived experience who can bring patient focused learnings and experience as involved members of research teams. For researchers who are a part of this Conference, how are you including patient partners in the research that you are doing? If you were to include patient partners in your research, how would you do that? If this is something that you are doing already or something that you would like to start to do, I would like to encourage you to reach out to OICR to share your experiences or begin a discussion about how the OICR PFAC can help to bring the patient partner voice to your work.
Thank you for this opportunity to be able to share some patient reflections from Day 1 of the Conference. You can also read patient reflections from Day 2 below.
Day 2 opened with Dr. David O’Neill, President of FACIT, described the need for establishing Ontario in a position of strength in the area of oncology research and the importance of initiatives such as Ontario First commercialization. As patient partners, we absolutely agree that we need to work diligently to ensure that patients are getting early access to experimental diagnostics, imaging and treatments. Building pathways for translating health intellectual property will create a positive feedback loop – encouraging even more research and research commercialization here in Ontario to continuously grow the promising pipeline of high-quality oncology innovations. It is about a positive impact on research, health systems, and the economy.
In our Patient Partner debrief today, we talked about the breadth and quality of research presented today, and at the Conference overall. We can hear the excitement and enthusiasm as presenters talk about their research and the science. This enthusiasm is palpable and in turn excites patients.
We see great examples of collaboration that is happening provincially, nationally and internationally. Collaboration is paramount and we applaud the sharing of research and the creation of multi-disciplinary teams to push science forward and provide the right treatments to the right patients at the right time.
Patient partners are excited by what we learned today about research on:
- The use of novel imaging technologies to investigate cancer from the single cell level to understand different disease sub-groups and possible response to treatment.
- The production of radiolabelled molecules for imaging and therapy – pushing forward understanding of patient stratification, disease response monitoring, drug development and imaging as predictive biomarkers of disease response.
- The better understanding of diseases like pancreatic cancer through clinical trials to improve outcomes for patients.
Exciting developments were also shared about international data sharing, ICGC-ARGO and platforms for Big Data. And also the longitudinal understanding of cancer through CanPath to support studies focused on early detection.
We also heard about the importance of including health technology assessment early in the research process, especially within the precision medicine landscape, and how we can create a learning healthcare system to generate and apply real world evidence.
During the open session on patient partnership, the discussion was wide ranging. We talked about the importance of integrating patient partners in research. Cancer forces patients to walk a tightrope and helping researchers understand that bigger picture is critical. Patient partners provide a human face to research.
We also talked about the importance of equity, diversity and inclusion in research and patient partnership and the importance of ensuring that treatments, clinical trials, and research are representative of all Canadian communities.
We discussed how we communicate to patients about science, clinical trials, and research findings. There is an obvious importance of talking about the successes of research; however, it is important to discuss the failures that also occur. The scientific process is not only about the successes. It is critical that we do a better job of helping each other understand where research fails and how we use that knowledge to understand where to go next.
Ideal patient partnership engagement has many forms. It is about ensuring that patients are involved early in the project, that their role is defined and understood, the involvement is built on trust and respect, and that there is a platform for open two-way conversation. If you are unsure with how to integrate patient partners within your research, the most important thing that you can do is try. If you need help with integrating patient partners into your research, please reach out to OICR and the Patient and Family Advisory Council will be happy to help.
Thank you for this opportunity to be able to share some patient reflections from Day 2 of the Conference.
March 9, 2021
The funding will support projects ranging from drug discovery to cancer stem cells
Seven OICR-affiliated researchers have been awarded $6.6 million in funding from the Canadian Institutes for Health Research (CIHR) through its Project Grants program, which is designed to capture ideas with the greatest potential to advance health and research. The funded projects will help support key OICR research in drug discovery, pancreatic cancer, immunotherapy, genomics and circulating tumour DNA, and cancer stem cells.
Dr. Rima Al-Awar
Head, Therapeutic Innovation and Drug Discovery, OICR
The Discovery and Optimization of NUAK Inhibitors: A Novel Approach to Target Hippo Pathway Driven Cancers
Dr. Kieran Campbell
OICR Affiliate, Scientist & Principal Investigator, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital
Characterizing immune evasion in pancreatic adenocarcinoma: an integrative computational and experimental approach to understanding aberrant antigen presentation
Dr. Naoto Hirano
OICR Clinician Scientist, Senior Scientist, Princess Margaret Cancer Centre
Development of TCR-engineered T cells against novel NY-ESO-1 epitopes for the treatment of triple negative breast cancer
Dr. Hartland Jackson
OICR Investigator, Investigator, Lunenfeld-Tanenbaum Research Institute, Sinai Health
Targeting chemotherapy resistant multi-cellular environments in pancreatic cancer
Dr. Courtney Jones
OICR Investigator, Senior Scientist, Princess Margaret Cancer Centre
Characterization and Targeting of SIRT3 in Acute Myeloid Leukemia Stem Cells
Dr. Faiyaz Notta
OICR Associate, Co-Lead, OICR PanCuRx Translational Research Initiative, Scientist, Princess Margaret Cancer Centre
Impact of copy number imbalances in mutant KRAS on pancreatic cancer chemoresistance and metastases
Dr. Trevor Pugh
Senior Investigator and Director, Genomics, OICR
Understanding inevitable relapse of multiple myeloma following highly-effective anti-BCMA treatment
March 1, 2021
Research breakthrough paves way for more cancer patients to benefit from immunotherapy, regardless of ancestry
OICR Investigator, Dr. Naoto Hirano, expands arsenal of immunotherapy technologies, opening new frontiers in immunotherapy for cancer patients and beyond
Adoptive cell therapy is a promising cancer treatment that uses our immune system to eliminate cancer cells. These treatments, however, are only effective for a small subset of individuals with specific types of cancer and specific inherited genes. Dr. Naoto Hirano’s recent breakthrough paves the way for novel immunotherapies to help more patients, regardless of their genetic ancestry, live longer and healthier lives.
In a study published in Nature Biotechnology, Hirano and his collaborators developed a new technology that rigorously and robustly identifies the immune cells that are capable of recognizing and eliminating cancer cells. This technology allows researchers to develop new immunotherapies for cancer patients that are not limited by the differences – or heterogeneity – of tumour cells, thus expanding the potential impact of immunotherapy for patients around the world.
Hirano’s technology applies to an immunotherapy approach called T cell receptor (TCR) gene therapy that is based on genetically-engineered immune cells (T cells) recognizing and binding to specific molecules, called peptide-loaded human leukocyte antigens (HLA), on the surface of cancer cells. Although there has been progress in TCR therapy, there are more than 28,000 different variations of HLA found in humans and current TCR therapies only work for a few of these variations.
“Historically, TCR treatments have been developed for those who had the most common and well-studied HLA alleles, which often meant that these immunotherapies only worked for people from Caucasian ancestry,” says Hirano, who is a Senior Scientist at the Princess Margaret Cancer Centre and OICR Clinician Scientist. “It was an important goal for us to develop a technology that could work for a broad range of HLA alleles. We’re proud of what we developed because it could help many more cancer patients in the future.”
The technology presented in this study involves a methodology that can – in a single step at a low expense – form a functional protein structure, called a dimer, that is comprised of any peptide and HLA molecule, regardless of type, and can bind to and identify a variety of T cells. The method improves the binding affinity between T cells and HLA molecules nearly 200-fold relative to prior methods, which could allow researchers to better identify and engineer the T cells for novel immunotherapies.
The technology has been licensed to TCRyption Inc. for further development, translation, and large-scale implementation. In the future, it may be applied to fields other than cancer research and care, including autoimmune diseases such as rheumatoid arthritis and type 1 diabetes.
“I’m grateful for the cancer research community’s support over the years, which has enabled me to focus on important and challenging issues,” says Hirano, who was named the University Health Network’s Inventor of the Year last year for developing these analysis techniques. “Only with the support for rigorous experimentation, deep expertise, and innovative thinking, were we able to make this breakthrough.”
Note: N.H. has received research funding from Takara Bio and served as a consultant for Takara. The University Health Network has filed a patent application related to this study on which N.H. is named as a lead inventor. N.H. is cofounder and has equity in TCRyption to which the technologies used in this study have been licensed.
February 23, 2021
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.”
This morning, I joined two of our all-star MPPs @ninatangri & @SkellyHamilton to check out the innovative work being done by @OICR_news at @MaRSDD.— Doug Ford (@fordnation) February 23, 2021
We’re working hard to ensure Ontario continues to have one of the largest #LifeSciences sectors anywhere in the world. #OntarioMade pic.twitter.com/DRGHqqzcpR
Excellent work being done by this sector. Very innovative and providing great solutions https://t.co/495GMU7S3Z— Nina Tangri (@ninatangri) February 23, 2021
February 4, 2021
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.
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.”
“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.
February 3, 2021
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.
- 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.
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January 4, 2021
Researchers discover brain cancer may develop when tissue healing runs amok, uncovering new approaches to combat the deadly disease
The healing process that follows a brain injury, such as an infection or a stroke, could spur tumour growth when the new cells generated are derailed by mutations, Toronto scientists have found. This discovery could lead to new therapy for glioblastoma patients who currently have limited treatment options with an average lifespan of 15 months after diagnosis.
The findings, published today in Nature Cancer, were made by an interdisciplinary team of researchers from OICR, the University of Toronto’s Donnelly Centre for Cellular and Biomolecular Research, The Hospital for Sick Children (SickKids) and the Princess Margaret Cancer Centre who are also on the pan-Canadian Stand Up to Cancer (SU2C) Canada Dream Team that focuses on a common brain cancer known as glioblastoma.
“Our data suggest that the right mutational change in particular cells in the brain could be modified by injury to give rise to a tumour,” says Dr. Peter Dirks, senior author of the study, OICR-supported researcher, Dream Team co-leader, and Head of the Division of Neurosurgery and a Senior Scientist in the Developmental and Stem Cell Biology program at SickKids. “We’re excited about what this tells us about how cancer originates and grows and it opens up entirely new ideas about treatment by focusing on the injury and inflammation response.”
The research group, led in part by OICR and Princess Margaret’s Dr. Trevor Pugh, applied the latest single-cell RNA sequencing and machine learning technologies to map the molecular make-up of the glioblastoma stem cells (GSCs), which Dirks’ team previously showed are responsible for tumour initiation and recurrence after treatment.
Equipped with these single-cell analysis methods, the research group was able to accurately differentiate and study different types of tumour cells. Through analyzing 26 tumours and nearly 70,000 cells, they found new subpopulations of GSCs that bear the molecular hallmarks of inflammation.
This finding suggests that some glioblastomas may start to form when the normal tissue healing process is derailed by mutations, possibly even many years before patients become symptomatic, Dirks says. Once a mutant cell becomes engaged in wound healing, it cannot stop multiplying because the normal controls are broken and this spurs tumour growth, according to the study.
The study’s authors, including co-leading researcher, Dr. Gary Bader from the Donnelly Centre as well as graduate students including Owen Whitley and Laura Richards, are now working to develop tailored therapies target these different molecular subgroups.
“There’s a real opportunity here for precision medicine.” says Pugh, who is Director of Genomics at OICR and the Princess Margaret Cancer Centre. “To dissect patients’ tumours at the single cell level and design a drug cocktail that can take out more than one cancer stem cell subclone at the same time.”
In addition to funding from the Stand Up To Cancer Canada Cancer Stem Cell Dream Team: Targeting Brain Tumour Stem Cell Epigenetic and Molecular Networks, the research was also funded by Genome Canada, the Canadian Institutes for Health Research, the Ontario Institute for Cancer Research, Terry Fox Research Institute, the Canadian Cancer Society and SickKids Foundation.
December 3, 2020
A holiday message from Dr. Laszlo Radvanyi, OICR’s President and Scientific Director:
This year has presented immense challenges and hardships for people around the world, including cancer patients, researchers, clinicians and many others in the OICR community.
As I reflect on what has transpired over 2020, I think the most lasting memory will be the amazing adaptability of our staff, funded researchers, leadership and partners that has allowed us to continue pressing ahead in the fight against cancer, all while contributing to COVID-19 research and staying safe. I thank everyone for their remarkable contributions to cancer research during this difficult time and for being part of the historic scientific campaign against COVID-19, while keeping our cancer focus solidly intact.
While the year did not go as anyone planned, we have continued to make a difference for cancer patients by advancing cutting-edge solutions for preventing, screening, diagnosing and treating cancer. Of particular note this year was the Pan-Cancer Analysis of Whole Genomes (PCAWG) project coming to its climax, generating astounding insights into cancer genomics that are fueling entirely new ways to approach cancer such as developing new tools and approaches to interrogate the role of non-coding regions of the genome. This project is emblematic of the efforts of OICR researchers across our programs to collaborate and find truly novel solutions to the many challenges we face in improving the lives of cancer patients. The scientific network of investigators we fund has also made tremendous contributions, including advancing new drug targets and cell therapy approaches against cancer as well as inroads in understanding cancer therapeutic resistance via cancer stem cells and uncovering novel molecular subsets of cancers, such as pancreatic cancer.
Earlier this year a positive international external review found that OICR is making a true impact and is on the right track, having built a firm foundation to reinforce our model and take the next steps in furthering our impact. Through consultations with our stakeholders, we have developed a bold and visionary new strategic plan that will expand our focus on early cancer detection and intervention as well as strengthen our growing and successful drug discovery efforts. This plan builds not only on our current momentum, but also further deepens collaborations with our provincial, national and global partners.
Of course, our progress thus far would not be possible without the support of the Government of Ontario through the Ministry of Colleges and Universities – I thank them for their continued investment in made-in-Ontario cancer innovations and belief in our vision of “cancer solved together”. I also thank our partners in cancer research and care at cancer centres, research institutes and universities across Ontario for their continued collaboration and engagement. Together we have continued to perform world class research, improve cancer care and bring real economic benefits to Ontario’s economy.
In closing, I note that many of us will not be able to celebrate the holidays as we have in years past. While this is unfortunate, we must focus on the good we are doing for ourselves, our loved ones and our communities by doing our part for public health. I wish happy holidays and a happy new year to all as we look forward to a much brighter year ahead. Please take care and stay safe.
Dr. Laszlo Radvanyi
President and Scientific Director, OICR
November 30, 2020
Researchers find 3-D structure of the genome is behind the self-renewing capabilities of blood stem cells
OICR-funded researchers open a new path to discover drivers of chemotherapy resistance and cancer relapse
Stem cells have the capability to self-renew and create other types of cells, but not all stem cells are equal. OICR-supported researchers at the Princess Margaret Cancer Centre, Drs. Mathieu Lupien and John Dick, have discovered a new way to distinguish the self-renewing capabilities of stem cells, revealing new ways to study the origins of cancer and cancer recurrence.
In their recently published study in Cell Stem Cell, Lupien, Dick and collaborators identified how some blood – or hematopoetic – stem cells can self-renew but others lose that ability. They found differences in the three-dimensional structure of the genetic information between different stem cell types.
DNA within each human cell, including stem cells, is coiled and compacted in a highly regulated way into structures called chromatin. Depending on how DNA is compacted into chromatin, some regions of DNA are accessible to gene-expressing cellular machinery while some aren’t, influencing how genes are expressed and how a cell may behave. The study group identified that this chromatin accessibility is a key component of a cell’s self-renewing capabilities and “stemness”.
“Enabled by the latest technologies, we found that the pattern of closed – or inaccessible – regions of DNA and the open or accessible regions differ between the long-term self-renewing stem cells and other more mature blood cell populations” says Lupien, Senior Scientist at the Princess Margaret Cancer Centre, Associate Professor at the University of Toronto and OICR Investigator.
The study discovered that the self-renewal capabilities are specifically linked to parts of the genome that bind a protein that is responsible for chromatin folding, called CTCF. As cancer researchers, Lupien and Dick are now applying these discoveries made in normal stem cells to study cancer stem cells. It is thought that if a cancer treatment cannot eliminate the cancer’s stem cells, these surviving self-renewing cells can give rise to recurrent tumours. With a better understanding of cancer stem cells, researchers can investigate the roots of cancer and how to potentially target or manipulate the mechanisms behind self-renewal.
This breakthrough study was made possible by Lupien’s expertise in epigenetics, the field that studies gene expression, Dick’s expertise in stemness and blood development, and the contributions of collaborators and trainees, including Drs. Naoya Takayama and Alex Murison who led the wet lab assays and bioinformatics analyses respectively.
“Understanding how stemness is controlled is key to being able to harness the power of stem cells for cell-based therapies, but also to understand how malignant cells perturb stemness to allow the cancer stem cells to continue to propagate tumor growth,” says Dick, Senior Scientist at the Princess Margaret Cancer Centre, Professor at the University of Toronto and lead of OICR’s Acute Leukemia Translational Research Initiative. “We look forward to furthering our understanding of hematopoiesis and bringing these insights closer to clinical application.”
November 18, 2020
Ontario cancer research leaders, Drs. Geoff Fong, Trevor Pugh and Lincoln Stein recognized as Highly Cited Researchers by Clarivate for their influential work
OICR is proud to celebrate the recognition of three Ontario cancer research leaders, Drs. Geoffrey Fong, Trevor Pugh and Lincoln Stein as Clarivate’s Highly Cited Researchers of 2020. This recognition demonstrates the incredible global impact of Ontario’s researchers and underscores the importance of sharing knowledge for greater progress around the world.
Fong, Pugh and Stein, who are senior OICR investigators and leaders, have led several international scientific collaborations that have uncovered valuable knowledge and informed disease control and management strategies in Canada and around the world.
- Dr. Geoffrey Fong leads the International Tobacco Control Policy Evaluation Project, which conducts cohort studies on the implementation of evidence-based tobacco control policies. The ITC Project has conducted studies in 29 countries, inhabited by more than 50 per cent of the world’s population.
- Dr. Trevor Pugh, who was recently named one of Canada’s Top 40 Under 40, leads highly-collaborative genomics studies that are focused on applying sequencing analysis in the clinic. His landmark cancer genome studies have advanced research across different cancer types and his work continues to make precision cancer medicine a reality.
- Dr. Lincoln Stein has led large international data sharing consortia, such as the International HapMap Consortium and the International Cancer Genome Consortium, which have led to highly-cited scientific tools and discoveries. The tools, data and knowledge resulting from these consortia have been used by tens of thousands of people around the world.
“We’re proud that cancer researchers here in Ontario are making a worldwide impact that will improve the prevention, diagnosis and treatment of cancer,” says Dr. Laszlo Radvanyi, President and Scientific Director of OICR. “I congratulate Drs. Fong, Pugh and Stein on this well-deserved recognition.”
The highly-anticipated annual list identifies researchers who demonstrated significant influence in their field or fields through the publication of multiple highly cited papers during the last decade. Their names are drawn from the publications that rank in the top one per cent by citations for field and publication year in the Web of Science citation index. Clarivate’s methodology draws on the data and analysis performed by bibliometric experts and data scientists at Clarivate’s Institute for Scientific Information.
The full 2020 Highly Cited Researchers list and executive summary can be found online here.
November 5, 2020
Study finds that every month delay in cancer treatment can raise risk of death by around 10 per cent
Research led by Dr. Timothy Hanna suggests that minimizing delays to treatment could improve cancer survival rates
Many countries have needed to defer cancer surgeries, radiotherapy and other treatments through the COVID-19 pandemic, which has brought the impact of treatment delays into sharp focus. In a study published today in The BMJ, Dr. Timothy Hanna and collaborators report that people whose cancer treatment is delayed by even four weeks have in many cases a six to 13 per cent higher risk of dying – a risk that keeps rising the longer their treatment does not begin.
“We know that delay matters and now we understand how much it matters,” says Hanna, Radiation Oncologist at the Cancer Centre of Southeastern Ontario, Faculty of Queen’s Cancer Research Institute, OICR Clinician Scientists and lead of the study. “With these data, we can now quantify the impact of treatment delays – including those that we’re experiencing now throughout the COVID-19 pandemic.”
The research group reviewed and analyzed relevant studies from around the world that were published over the last two decades. They found that there was a significant impact on a person’s risk of death if their treatment was delayed, whether the treatment was surgical, chemotherapy or radiotherapy. They observed this impact across all seven types of cancer analyzed – breast, bladder, colon, rectum, lung, cervix and head and neck cancers.
For example, with cancer surgery, they saw a six to eight per cent increase in the risk of death for every four-week treatment delay, meaning that a three-month delay could increase the risk of death by about 25 per cent. The impact was even greater for specific treatments – such as bowel cancer chemotherapy – where a three-month delay could cause a 44 per cent increase in risk of death.
“As we move towards the second COVID-19 wave in many countries, the results emphasize the need to prioritize cancer services including surgery, drug treatments and radiotherapy as even a four-week delay can significantly increase the risk of cancer death,” says Dr. Ajay Aggarwal, co-lead of the study from King’s College London and the London School of Hygiene and Tropical Medicine.
Hanna hopes this study will help inform cancer treatment backlog management and prioritization. His prior work on prioritizing treatment during COVID-19, published in Nature Reviews Clinical Oncology, has been incorporated into health system planning and management in Ontario and around the world.
“The impact of cancer treatment delays will persist long after the threat of this pandemic subsides,” says Hanna. “As a clinician, a patient, an administrator or a decision-maker in our cancer care system, these results should encourage us all to put resources and efforts in place to minimize system level delays in cancer treatment.”